# <span class=strong>Reception and Poster Session</span><br><br/><br/><b>Poster submissions welcome from all participants</b><br><br/><br/><a href=http://www.ima.umn.edu/visitor-folder/contents/workshop.html#poster><b>Instructions</b></a>

Monday, May 18, 2009 - 4:00pm - 6:30pm

Lind 400

**A Cartesian treecode for screened Coulomb interactions**

Robert Krasny (University of Michigan)

A treecode algorithm is presented for evaluating the electrostatic potential in charged particle systems undergoing

screened Coulomb interactions in 3D. The method uses a far-field Taylor expansion in Cartesian coordinates to compute particle-cluster interactions. The Taylor coefficients are evaluated using new recurrence relations which permit efficient computation of high order approximations. Two types of clusters are considered, uniform cubes and adapted rectangular boxes. The treecode error, CPU time, and memory usage are reported and compared with direct summation for randomly distributed particles inside a cube, on the surface of a sphere, and on an 8-sphere configuration. For a given order of Taylor approximation, the treecode CPU time scales as O(NlogN) and the memory usage scales as O(N), where N is the number of particles in the system. Results show that the treecode is well suited for non-homogeneous particle distributions as in the sphere and 8-sphere test cases. This is joint work with Peijun Li (Purdue) and Hans Johnston (U. Mass - Amherst), and has appeared in J. Comput. Phys., vol. 228 (2009) 3858-3868.**Molecular dynamics simulation of Liquid methyl chloride**

with a treecode Ewald summation method

Henry Boateng (University of Michigan)

We will present results on the application of the treecode method to the computation of the real space part of the Ewald sum in molecular dynamics simulation. We show that for reasonable parameters, the treecode speeds up the Ewald sum for large systems and reproduces the structural and dynamical properties of the liquid within error bars.**Analysis of folding pathways in model peptides**

Krzysztof Kuczera (University of Kansas)

Molecular dynamics and replica-exchange simulations are performed for a model

peptide, NAcetyl-ALA5-Amide, using several popular force fields. We obtain helix populations,

melting curves, folding and nucleation times. The distributions of conformer populations are used to measure folding cooperativity. Finally, a statistical analysis of the sample of helix-coil transition paths is performed, uncovering interesting microscopic properties of the folding process.**Liquid-liquid critical point in supercooled silicon**

Srikanth Sastry (Jawaharlal Nehru Centre for Advanced Scientific Research(JNCASR))

Liquid silicon has previously been shown to exhibit a liquid-liquid

transition in the supercooled state at zero pressure, using computer

simulations employing the Stillinger-Weber (SW) potential. The

associated liquid-liquid (LL) critical point lies at negative

pressures. Computer simulation evidence of such a negative pressure

critical point is presented, along with characterization of structural

and dynamical properties of the liquid in the vicinity of the critical

point. Preliminary results are presented on crystal nucleation, which

near the liquid-liquid critical point will be governed by the

interplay of critical density fluctuations and nearly tetrahedral,

crystal-like, local order in the liquid that grows with decreasing

density.**What is a good thermostat?**

Emad Noorizadeh (University of Edinburgh)

Molecular dynamics perturbs Hamiltonian dynamics in order to compute

correct ensemble averages. On the other hand computation of dynamical

averages such as autocorrelation functions requires the molecular

dynamics trajectory to be close to a microcanonical dynamics. This

suggest that, ideally we would like to have a small growth of the

perturbation and a fast rate of convergence to the Boltzmann-Gibbs

measure. Here we show how to achieve such a gentle thermostat by

combining a deterministic method (e.g. Nose-Hoover) with Langevin

dynamics. We use the concept of hypoellipticity of the forward

Kolmogorov equation, and Hörmander's condition, to investigate the existence of a unique invariant measure, which

implies ergodicity. We compare different methods in numerical

experiment.

This is a joint work with Ben Leimkuhler (School of Mathematics, University of

Edinburgh) and Florian Theil (Mathematics Institute, University of Warwick).

Reference:

[1] B. Leimkuler, E. Noorizadeh and F. Theil, J. Stat. Phys. 135, 261-277 (2009)**Fast path integral simulations using ring polymer contraction**

Thomas Markland (University of Oxford)

A quantum simulation of an imaginary time path integral typically requires around n times more computational effort than the corresponding classical simulation, where n is the number of ring polymer beads (or imaginary time slices) used in the calculation. However, this estimate neglects the fact that the potential energies of many systems can be decomposed into a sum of rapidly-varying short-range and slowly-varying long-range contributions. For such systems, the computational effort of the path integral simulation can be reduced considerably by evaluating the long-range forces on a contracted ring polymer with fewer beads than are needed to evaluate the short-range forces. Using this approach it is shown that, for a typical application to a flexible model of liquid water, near classical simulation times can be achieved while still obtaining the exact path integral result.**The string method as a dynamical system**

Maria Cameron (Courant Institute of Mathematical Sciences)

This project is devoted to the theoretical analysis of the

zero-temperature string method to identify minimum

energy paths (MEP's) on a given energy landscape. The MEP's are curves

connecting local minima on the energy landscape which are everywhere

tangent to the gradient of the potential except possibly at critical

points. In practice, MEP's are mountain pass curves that play a special role

e.g. in the context of rare reactive events that occur when one

considers a steepest descent dynamics on the potential perturbed by a

small random noise. The string method aims at identifying MEP's by

moving each point of the curve by steepest descent on the energy landscape.

Here we address the question of whether such a curve evolution

necessarily converges to a MEP. Surprisingly, the answer is no, for

an interesting reason: MEP's may not be isolated, in the sense that

there may be families of them that can be continuously deformed into

one another. This degeneracy is related to the presence of critical

points of

Morse index 2 or higher along the MEP. In this paper, we elucidate

this issue and characterize completely the limit set of a curve

evolving by the string method. We establish rigorously that the limit

set of such a curve

is again a curve when the MEP's are isolated. We also show under the

same hypothesis

that the string evolution

converges

to an MEP. However, we also identify and classify situations where the limit set

is not

a curve and may contain higher-dimensional

parts. We present a collection of examples where the limit set of a

path contains a 2D region, a 2D surface, or a 3D body. In some of

our examples the evolving path wanders around without converging to its limit set.

In other examples it fills a region, converging to its limit set

which is not an MEP.**An image-based reaction field method for electrostatic interactions in molecular dynamics simulations of aqueous solutions**

Yuchun Lin (University of North Carolina)

Joint work with

Andrij Baumketner^{a}, Wei

Cai^{b},

Shaozhong Deng^{b}, Donald

Jacobs^{a}, and Zhenli

Xu^{b}.

A new solvation model is proposed for simulations of

biomolecules in aqueous solutions that combines the strengths

of explicit and implicit solvent representations. Solute

molecules are placed in spherical cavities filled with explicit

water, thus providing microscopic detail where it is needed.

Solvent outside of the cavities is replaced with a dielectric

continuum whose effect on the solute is modeled through the

reaction field corrections. With this explicit/implicit model,

the electrostatic potential represents a solute molecule in an

infinite bath of solvent, thus avoiding unphysical interactions

between periodic images of the solute commonly used in the

lattice-sum explicit solvent simulations. For improved

computational efficiency, our model employs an accurate and

efficient multiple-image method to compute reaction fields

together with the fast multipole-expansion technique for the

direct Coulomb interactions. To minimize the surface effects,

periodic boundary conditions are employed for non-electrostatic

interactions. The proposed model is applied to study liquid

water. The effect of main geometric parameters of the model,

which include the size of the cavity, the number of charge

images used to compute reaction field and the thickness of the

buffer layer, is investigated in comparison with the

particle-mesh Ewald simulations as a reference. An optimal set

of parameters is obtained that allows for a faithful

representation of many structural, dielectric and dynamic

properties of the simulated water, while maintaining manageable

a computational cost. With predicable increasing accuracy of

the multiple-image charge representation of the reaction field,

it is concluded that the proposed model achieves convergence

with only one image charge in the case of pure water. Future

applications to pKa calculations, conformational sampling of

solvated biomolecules and electrolyte solutions are briefly

discussed.^{a}: Department of Physics and Optical Science, University of

North Carolina at Charlotte, Charlotte, NC 28223, United

States^{b}: Department of Mathematics and Statistics, University of

North Carolina at Charlotte, Charlotte, NC 28223, United

States**Interface method and Green's function based Poisson–Boltzmann**

equation solver and interface technique based molecular

dynamics

Weihua Geng (University of Michigan)

Implicit solvent models, which treat the solvent as a macroscopic

continuum while admitting a microscopic atomic description for the

biomolecule, are efficient multiscale approaches to complex, large scale

biological systems. We summarize our recent advances in mathematical

methods for the Poisson-Boltzmann (PB) Model.

These include rigorous mathematical treatments of interface jump

conditions, surface geometric singularities, charge singularities, and

associated electrostatic force computation for molecular dynamics.**Counting for rigidity, flexibility and extensions via the pebble game algorithm**

– hinge predictions and allostery

Adnan Sljoka (York University)

In rigidity theory, specifically combinatorial rigidity, one can simply count

vertices and edges (constraints) in a graph and its subgraphs to determine the

rigidity and flexibility of a corresponding framework. The 6V–6 counting

condition for 3-dimensional body-hinge structures (modulo molecular

conjecture), and a fast `pebble game' algorithm which tracks the underlying

count in the multigraph, have led to the development of the program FIRST, for

rapid analysis of the rigidity and flexibility of proteins and other large

macromolecular structures such as viral capsids. An important recent

application of FIRST is the introduction of the program FRODA which is a Monte

Carlo based geometric simulation technique, which uses the predictions of rigid

and flexible regions from FIRST to simulate the motions of proteins. FRODA can

run up to a million times faster than the Molecular Dynamics Simulations. We

will give a brief description and illustration of the 6V – 6 pebble game

algorithm. We further extend the pebble game algorithm to quantify the relative

degrees of freedom of a specified region (core) in the multigraph and identify

the regions that are relevant as constraints with respect to the core and those

regions that are irrelevant and that can be ignored both for focus and for speed

of simulations. With these new extensions (algorithms) we have developed a novel

approach in detecting hinge motions between protein domains. We can accurately

locate hinge points using only a single protein structure. Other application of

this work is to detect regions required for allostery; and the rigidity impact

of mutation studies. We present examples of these new extensions along with

biological applications.**Kinetic Monte Carlo simulation of the Yttria Stabilized**

Zirconia (YSZ) fuel cell

Kah Chun Lau (George Washington University)

A Kinetic Monte Carlo (KMC) model is developed to simulate non-symmetrically the cathode side of a Yttria Stabilized Zirconia (YSZ) fuel cell, in order to translate experimental, and ultimately theoretical rates into an atomistic model of

the fuel cell. The KMC model consists of a set of several electrochemical reaction rates, adopted from experiments and

first-principles calculations. The KMC simulations are used to model these simultaneously occurring events, and to determine potential limitations in cathode/YSZ performance. The focus of this work is ionic current density (J), studied as a function of various physical parameters: oxygen partial pressure, external applied bias voltage, operating temperature, dopant concentration, relative permittivity of YSZ, and geometrical features of the YSZ electrolyte. This simple model can be used as a baseline to translate elementary electrochemical reaction rates into atomistic simulations of a working solid oxide fuel cell cathodes, pertinent to the complete set of experimental operating conditions.**Investigating the importance of quantum mechanical recrossing effects in the**

rate coefficient of a condensed-phase reaction

Rosana Collepardo-Guevara (University of Oxford)

We have used the ring polymer molecular dynamics method to study the

Azzouz-Borgis model for proton transfer between phenol (AH) and trimethylamine

(B) in liquid methyl chloride. When the A-H distance is used as the reaction

coordinate, the ring polymer trajectories are found to exhibit multiple

recrossings of the transition state dividing surface and to give a rate

coefficient that is smaller than the quantum transition state theory value by an

order of magnitude. This is to be expected on kinematic grounds for a

heavy-light-heavy reaction when the light atom transfer coordinate is used as

the reaction coordinate, and it clearly precludes the use of transition state

theory with this reaction coordinate. As has been shown previously for this

problem, a solvent polarization coordinate defined in terms of the expectation

value of the proton transfer distance in the ground adiabatic quantum state

provides a better reaction coordinate with less recrossing. These results are

discussed in light of the wide body of earlier theoretical work on the

Azzouz-Borgis model and the considerable range of previously reported values for

its proton and deuteron transfer rate coefficients.**Microscopic flow around a diffusing particle**

Rodolphe Vuilleumier (École Normale Supérieure)

The fundamental model for diffusion is the Stokes-Einstein approach. It relates the diffusion coefficient to the friction coefficient which is in turn extracted from the hydrodynamic friction felt by a moving sphere in a liquid environment. The hydrodynamic flow around the sphere, commonly called Stokes flow, depends on the boundary conditions on the sphere. Two boundary conditions are usually considered: stick boundary conditions (no velocity at contact), as in the orginal approach, or slip boundary conditions (finite tangential velocity). As these two boundary conditions lead to different diffusion coefficient as a function of particle size, the usual way to investigate these from numerical simulations has been to compute the diffusion coefficient as a function of particle size. This leads for diffusion of Lennard-Jones particles to the suggestion of slip boundary conditions.

Here, we want to present a direct calculation of the microscopic velocity field around a diffusing particle from numerical simulations. This allow for comparison between the atomic model and the hydrodynamics approach. It is first demonstrated that the hydrodynamics flow is well recovered after only a few atomic radius from the tagged particle. However, two effects of the velocity fluctuations of the diffusing particle are evidenced. The boundary conditions are shown to include a finite normal velocity at contact, which would seem at first in contradiction with the non-penetrability of the particles but is an effect of fluctuations. Then, the flux of momentum in the flow is not determined solely by viscosity but also from the diffusion of the tagged particle.

This gives new insight in the diffusion process in liquids and in particular on the role of fluctuations at the atomic level. We will also try to show how this method could be also used in order to provide a more mechanistic description of the diffusion processes, in terms similar to reaction paths and transition states.**What ice can teach us about water interactions: a critical comparison of the performance of different water models**

Carlos Vega de las Heras (Universidad Complutense de Madrid)

Coauthors: J. L. F. Abascal, M. M. Conde and J. L. Aragones.

The performance of several popular water models (TIP3P, TIP4P,

TIP5P and TIP4P/2005) is analysed.

For that purpose the predictions for ten different properties

of water are investigated, namely: 1. vapour-liquid equilibria

(VLE) and critical temperature; 2. surface tension; 3.

densities of the different solid structures of water (ices); 4.

phase diagram; 5. melting point properties; 6. maximum in

density at room pressure and thermal coefficients α and

κ_{T};

7. structure of liquid water and ice; 8. equation of state at

high pressures; 9. diffusion coefficient; 10. dielectric

constant. For each property, the performance of each model is

analysed in detail with a critical discussion of the possible

reason of the success or failure of the model. A final

judgement on the quality of these models is provided.

TIP4P/2005 provides the best description of almost all

properties of the list, with the only exception of the

dielectric constant. In the second position, TIP5P and TIP4P

yield an overall similar performance, and the last place with

the poorest description of the water properties is provided by

TIP3P.

The ideas leading to the proposal and design of the TIP4P/2005

are also discussed in detail. TIP4P/2005 is probably close to

the best description of water that can be achieved with a non

polarizable model described by a single Lennard-Jones

(LJ) site and three charges.**Exotic self-assembly scenarios in in two-dimensional dipolar mixtures**

with genetic algorithms

Gerhard Kahl (Technische Universität Wien)

Joint work with Julia Fornleitner, Federica LoVerso, and Christos N. Likos.

Genetic algorithms (GAs) are powerful tools, applied in many fields of

physics as they offer an efficient strategy in high-dimensional

optimisation problems. We have developed GA-techniques that allow us

to study equilibrium crystal structures in an unbiased and

parameter-free way. Recently we have refined our approach and extended

it to binary mixtures of dipolar particles in a two-dimensional

geometry, realisable in experiments via, e.g. magnetic colloids on a

pendant water droplet and exposed to an external field or,

equivalently, via polystyrene particles floating at an

oil-water-interface. Several non-trivial and exotic structures are

discovered and their dependence on concentration and size ratio of the

particle species is discussed.**Molecular dynamics simulations of binding of metal**

catalyst nanoparticles to carbon nanostructures by using ReaxFF

Carlos Sanz-Navarro (Autonomous University of Barcelona)

Carbon nanofibers have attractive properties as support materials for

catalyst nanoparticles. Nonetheless, there is still a need for more

insights into the actual atomic structure of a metal particle interacting

with carbon nanostructures. Detailed information on the local structure of

adhered nanoclusters is still inaccessible to direct experimental imaging.

In contrast, molecular dynamics (MD) simulations can provide atomistic

structural information of a nanoscale system. In addition, the Reax force

field (ReaxFF) aims to achieve a good compromise between accuracy and

computational efficiency. We present novel results of MD simulations of

platinum and nickel clusters adsorbed on several different carbon supports

by using the ReaxFF. This work seeks to give insights into recent

experiments that have found a high correlation between carbon

nanofiber-induced strain and catalytic activity of Ni clusters. We show

how some metal atoms are detached from the surface of the nanoclusters

over time scales unreachable by electronic-structure methods. The adatom

migration is compensated by a rearrangement of the atomic structure of the

cluster. We also show differences in the bond length distribution of the

cluster when adsorbed to carbon nanocones with different radii as well as

differences found between Pt and Ni clusters. In addition, we brief on

preliminary results on diffusion of oxygen, hydrogen and carbon atoms over

the adsorbed cluster.**Simulations of phase transitions for fluids in pores using dynamic mean field theory**

Peter Monson (University of Massachusetts)

We consider the mean field kinetic equations describing the relaxation dynamics of a lattice model of a fluid confined in a porous material. The dynamical theory embodied in these equations can be viewed as a mean field approximation to a Kawasaki dynamics Monte Carlo simulation of the system, as a theory of diffusion, or as a dynamical density functional theory. The solutions of the kinetic equations for long times coincide with the solutions of the static mean field equations for the inhomogeneous lattice gas. The approach is applied to a lattice gas model of a fluid confined in a finite length slit pore open at both ends and in contact with the bulk fluid at a temperature where capillary condensation and hysteresis occur. The states emerging dynamically during irreversible changes in the chemical potential are compared with those obtained from the static mean field equations for states associated with a quasistatic progression up and down the adsorption/desorption isotherm. In the capillary transition region the dynamics involves the appearance of undulates (adsorption) and liquid bridges (adsorption and desorption) which are unstable in the static mean field theory in the grand ensemble for the open pore but which are stable in the static mean field theory in the canonical ensemble for an infinite pore.**Effective dynamics for reaction coordinates**

Frédéric Legoll (École Nationale des Ponts-et-Chaussées)

Computing canonical averages is a standard task in molecular dynamics. The main difficulty comes from the existence of metastable states. In order to facilitate sampling, and to obtain a better understanding of the system, low-dimensional reaction coordinates are often introduced. The statistics of these reaction coordinates are completely described by the associated free energy. However, the link between free energy barriers and dynamical informations, such as transition rates from one well to another, is less clear.

In this work, we design an effective, low-dimensional, dynamics on the reaction coordinate, which is a good approximation of the reference evolution, computed from the dynamics of the complete system. The accuracy of the effective dynamics is supported by error estimators. We also show, on a simple system, that our dynamics correctly reproduces the residence times in the wells.**Competing quantum effects in liquid water**

Scott Habershon (University of Oxford)

Numerous simulation studies comparing the classical and quantum molecular

dynamics of simple empirical liquid water models have suggested that quantum

mechanical zero point energy and tunnelling increase the rates of translational

and orientational dynamics by a factor of about 1.4. In this work, we suggest

that the magnitude of this effect has been overestimated, principally as a

result of the use of either rigid water models or models in which

intramolecular flexibility is described by simple harmonic functions.

We have developed a new simple point charge model for liquid water, q-TIP4P/F,

in which O-H stretches are described by Morse-type functions. This model

correctly describes the liquid structure, translational diffusion and dipole

absorption frequencies in quantum (path integral-based) simulations, and also

gives a good description of the temperature-dependence of the liquid density.

By comparing classical and quantum simulations, we find that quantum effects

increase the rates of translation diffusion and orientational relaxation by a

factor of 1.15, an effect which is smaller than observed in all previous

simulations, regardless of quantum simulation method or water model. We

attribute the small quantum effect in our water model to two competing

phenomena. First, zero point energy weakens the intermolecular hydrogen-bonding

network resulting in a less viscous liquid and faster diffusion. Second,

intramolecular zero point energy changes the average water monomer geometry,

resulting in a larger molecular dipole moment and stronger intermolecular

interactions. By comparison to other simulations of liquid water models, we

suggest that the small quantum effect in our model is associated with its

ability to reproduce a single broad O-H stretching band in the infra-red dipole

absorption spectrum.**Density matrix treatment of optical response with combined**

instantaneous and delayed dissipation: Adsorbates on solid surfaces

David Micha (University of Florida)

A density operator treatment has been developed for the

dissipative quantum dynamics of molecular systems in condensed matter.

It incorporates instantaneous and delayed rates of dissipation

originating in electronic and vibrational motions of the molecular

environment, respectively. The theory is applied here to the optical

response of the adsorbates CO/Cu(001) and Ag/Si(111).**Atomistic and heterogeneous multiscale modeling of CO-oxidation**

on metal(100) surfaces: From nanoscale ordering to mesoscale fronts

James Evans (Iowa State University)

A long-standing challenge has been to develop realistic atomistic-level

models of key surface reactions on single-crystal metal catalyst surfaces.

We have developed realistic multi-site lattice gas models for these

systems incorporating DFT energetics, and thus accurately describing

the complex nanoscale ordering of reactants [1]. Model behavior is

determined from KMC simulation. A second challenge is to incorporate

these atomistic models into a multiscale treatment of spatio-temporal

behavior on a much larger scale (of microns). This is achieved using

our Heterogeneous Coupled Lattice Gas (HCLG) simulation strategy [2],

together with a precise description of collective diffusion in these

mixed reactant adlayers. The result is a first-principles description

of reaction-diffusion front propagation [3].

[1] e.g., Liu, Evans, J. Chem. Phys. 124 (2006) 154705.

[2] Tammaro, Sabella, Evans, J. Chem. Phys. 103 (1995) 10277.

[3] Liu, Evans, Surf. Sci. (2009) doi:10.1016/j.susc.2008.10.058**Density-dependent analysis of nonequilibrium paths**

improves free energy estimates

David Minh (National Institutes of Health)

When a system is driven out of equilibrium by a time-dependent protocol that modifies the Hamiltonian, it follows a nonequilibrium path. Samples of these paths can be used in nonequilibrium work theorems to estimate equilibrium quantities, such as free energy differences. Here, we consider analyzing paths generated with one protocol using another one. It is posited that analysis protocols which minimize the lag, the difference between the nonequilibrium and the instantaneous equilibrium densities, will reduce the dissipation of reprocessed trajectories and lead to better free energy estimates. Indeed, when minimal lag analysis protocols based on exactly soluble propagators or relative entropies are applied to several test cases, substantial gains in the accuracy and precision of estimated free energy differences are observed.**Maximum flux transition path**

Juanfang Shen (Purdue University)Robert Skeel (Purdue University)Ruijun Zhao (Purdue University)

Given two metastable states A and B of a biomolecular system,

the problem is to compute a representative transition path by

which the mechanism of reaction can be analyzed. It is often

necessary to find such a path in collective variable space for

large biomolecular system. The maximum flux transition path (MFTP)

is defined as a path in collective variable space

that crosses each isocommittor at a point which (locally) has the

highest crossing rate of distinct reactive trajectories.

(Here the committor is defined to be the probability that a trajectory

at that point will reach B before A in collective variable space.)

Such an algorithm and computational performance will be discussed.**Computational alanine scanning of the alpha-lactamase**

inhibitor protein and TEM-1 alpha-lactamase complex

Hiqmet Kamberaj (University of Minnesota, Twin Cities)Yuk Sham (University of Minnesota, Twin Cities)

Protein association plays an essential role in many biological

processes. Understanding the general principles governing the

protein-protein interactions at the molecular level is of great

importance. In this study, we present a computational based alanine

scanning method that is used to elucidate the interactions between

alpha-lactamase and the alpha-lactamase inhibitor protein (BLIP). The

advantage of such approach is that it provides a direct

quantification of the specific per residue interactions between the

two proteins which can be directly validated with experimental

studies. Such analysis provides insight behind the structural and

energetic basis behind the molecular recognition process. Here, we

show the association between BLIP and TEM-1 is governed by clusters

of hot spots residues, which co-operatively modulate the formation

of the BLIP-TEM-1 complex. We also show that mutations in each

cluster do not influence the binding energy contribution of the

residues comprising other hot spots clusters, in agreement with

experimental results. The method presented here have broad range

application to study effect of mutation in drug binding as well as

de-novel protein design.**The impact of calcium on the dynamics and energetics of**

the complex between calmodulin and anthrax edema factor

Thérèse Malliavin (Centre National de la Recherche Scientifique (CNRS))

Joint work with E. Laine^{(1)}, J.D.

Yoneda^{(2)}, and A. Blondel^{(1)}.

Among the toxins secreted by Bacillus anthracis the edema factor EF, an adenylate

cyclase, provokes severe cellular dysfunction by accumulating cAMP from ATP. EF is

activated by calmodulin (CaM), involved in many calcium signaling pathways. The

stability of the EF-CaM complex depends on the level of calcium bound to CaM while

the architecture of the complex loaded with 2, 3 or 4 Ca2+ ions remains practically

unchanged. That is why modeling the electrostatic effect of Calcium through EF-

CaM structure is challenging.

Here, we aim at describing the calcium-induced changes in EF-CaM dynamics and

energetics through a consensual view of its residue network organization.

The analysis of molecular dynamics (MD) simulations of EF-CaM with 0,2 and 4 Ca2+

ions helped characterize CaM conformational plasticity and led to a model of the EF-

CaM interaction, in which CaM acts as a spring that maintains EF in an open active

conformation (Laine et al., 2008).

The complex was then analyzed (Laine et al.,2009) in order to extract simplified features describing its energetics and dynamics. The dynamics were analyzed using the LFA (Local Feature Analysis) (Zhang and Wrigers, 2006) and the generalized correlations (Lange and Grubmuller, 2006). These two approaches permitted to determine communication paths along the network of EF residues, from the helical domain to the domain CB. Beside, a new definition of the complex domains arose from the LFA analysis. This new definition, along with an approach derived from the energetic dependency maps (Hamacher et al, 2006), permitted to draw a simplified model of the energetic influences inside the complex. The variations of dynamics and energetics according to the level of Calcium complexation provide phenomenological reasons for the stability of the complex EF-CaM, by showing a disruption of the communication path or an imbalance of the energetic influences.

The computation of various dynamical covariances and energetic dependency maps

from the MD trajectories further raised the concept of residue network

connectedness. This connectedness quality provides a frame for unifying the

dynamics and energetics of the complex and a criterion for assessing its stability. .

Hamacher, K., J. Trylska, and J. McCammon. 2006. Dependency map

of proteins in the small ribosomal subunit. PLoS Comput. Biol. 2:e10.

Laine E, Blondel A, Malliavin TE (2009) Dynamics and energetics: a consensus analysis of the impact of calcium on EF-CaM protein complex.

Biophys J 96:1249-1263.

Laine E, Yoneda JD, Blondel A, Malliavin TE (2008) The conformational plasticity of calmodulin upon calcium complexation gives a model of its interaction with the oedema factor of Bacillus anthracis.

Proteins 71:1813-1829.

Lange OF, Grubmuller, H (2006) Generalized correlation for biomolecular dynamics. Proteins 62:1053-1061.

Zhang Z, Wriggers, W (2006) Local feature analysis: a statistical theory for reproducible essential dynamics of large macromolecules. Proteins 64:391-403.^{(1)}Unite de Bioinformatique Structurale,

Institut Pasteur, 28,

rue du Dr. Roux, F-75015 Paris, France^{(2)}

Programa de Posgraduac¸ao em Quimica Organica, Universidade

Federal Fluminense, Outeiro de S. Joao Batista s/n, 24020150,

Niteroi, RJ, Brazil.**Dynamical pathways to inactivation in the KcsA potassium channel**

Albert Pan (University of Chicago)

Ion channels gate the passage of ions through cell membranes

in response to external stimuli. In the case of the

archetypal potassium ion channel, KcsA, which opens and closes

upon a change in pH, recent experimental results have

demonstrated the existence of two physical gates: an

intracellular gate and a gate at the selectivity filter.

Lowering the pH opens the intracellular gate allowing ions to

pass. After the intracellular gate opens, however, the

channel can still inactivate by constricting the selectivity

filter and impeding the flow of ions even though the bottom

gate remains open. We use a combination of advanced

simulation techniques such as umbrella sampling, the string

method with swarms of trajectories, free energy perturbation

theory and Markov State models to probe the detailed mechanism

of this physiologically important process.**Pathwise accuracy and ergodicity of metropolized integrators for SDEs**

Nawaf Bou-Rabee (New York University)

Metropolized integrators for ergodic

stochastic differential equations (SDE) are exhibited which (i) are

ergodic with respect to the (known) equilibrium distribution of the

SDE and (ii) approximate pathwise the solutions of the SDE on

finite time intervals. Both these properties are demonstrated

including precise strong error estimates. It is also

shown that the Metropolized integrator retains these properties

even in situations where the drift in the SDE is nonglobally

Lipschitz, and vanilla explicit integrators for SDEs typically

become unstable and fail to be ergodic.**Concurrent triple-scale simulation of liquid water**

Matej Praprotnik (National Institute of Chemistry)

We present a triple-scale simulation of liquid water by concurrently coupling

the atomic, coarse-grained, and continuum descriptions of the liquid.

The triple-scale scheme, which is shown to correctly describe the

hydrodynamics, successfully sorts out the problem of large molecule

insertion in the hybrid particle-continuum simulations of molecular liquids.

The presented approach allows for efficient grand-canonical molecular dynamics

simulations of open systems involving an explicit solvent, e.g., liquid water.**Adaptive importance sampling strategies**

Gabriel Stoltz (École Nationale des Ponts-et-Chaussées (ENPC))

I study from a mathematical viewpoint a nonlinear stochastic dynamics (called the Adaptive Biasing Force method), which allows to adaptively bias a metastable dynamics by computing the free energy associated with a chosen slow direction. Some applications in computational statistical physics as well as Bayesian statistics are presented.**Some improvements of the ART method for finding transition pathways on potential energy surfaces**

Kimiya Minoukadeh (Ecole Nationale des Ponts et Chaussees)

The Activation-Relaxation Technique nouveau (ARTn) is an eigenvector following method for systematic search of saddle points and transition pathways on a given potential energy surface. We propose a variation of this method aiming at improving the efficiency of the local convergence close to the saddle point. We prove the convergence and robustness of this new algorithm. The efficiency of the method is tested in the case of point defects in body centered cubic iron.**Models of Chemical potential and the concept of atomistic**

embedding

Steven Valone (Los Alamos National Laboratory)

The concept of embedding some fragment in a larger system or reservoir appears everywhere in our scientific deliberations. Examples cover such diverse situations as an atom in a crystal, a functional group in a molecule, a molecular wire between a source and sink, or a protein in aqueous solution. Virtually every atomistic potential energy surface is built on one embedding strategy or another. This situation presents a difficulty for systems where charges are being transferred among fragments. Governance of transfer of charge is embodied in the concept of the chemical potential. When an embedded fragment and a reservoir can be readily identified, transfer of electrons between them can be described by an open ensemble. However, when interactions are strong as happens in crystals and molecules, the ensemble picture is not strictly applicable. Nevertheless, we still think in terms of open systems. Customary atomistic models use a linear model of chemical potential that is highly problematic. Here one strategy is presented to accommodate the open system point of view, while overcoming several limitations. That strategy focuses on decomposition into fragments of the many-body electronic hamiltonian itself, rather than decomposing the ground-state energy. The strategy produces a new, nonlinear model of chemical potential that has numerous ramifications for designing atomic potentials that can account for charge transfer.**The role of Arg517 in defining the fidelity of DNA**

polymerase lambda

Meredith Foley (New York University)

The maintenance of the genetic information in a cell is essential for its survival. DNA polymerases play a central role in this process since they replicate and repair DNA. These enzymes must be versatile and specific to accommodate the four combinations of the Watson-Crick base pairs while preventing errors such as incorrect nucleotide insertion.

DNA polymerase (pol) lambda is a mammalian enzyme involved in the base excision repair (BER) and non-homologous end-joining (NHEJ) DNA repair pathways. It is from the X-family of polymerases and is shaped like a hand with finger, palm, and thumb subdomains. It also has 8-kDa and BRCT domains that aid its participation in the repair pathways. Pol lambda has an unusual fidelity profile since it produces many deletion errors and relatively few base substitution errors.

Substantial experimental and computational work on a related enzyme, pol beta, has elucidated the conformational changes induced upon its binding the correct and incorrect nucleotide. These motions involve a large-scale rearrangement of the thumb and subtle motions of active-site protein residues that serve as gate-keepers in regulating pol beta's transition to an active state. Binding of the incorrect nucleotide hampers these transitions.

Here we describe dynamics simulations of pol lambda/DNA complexes to uncover the important motions and rearrangements prior to chemistry that account for pol lambda's specific error profile. As in pol beta, a series of active-site protein residues are hypothesized to modulate the assembly of the active site. However, DNA motion is also involved. Arg517 emerges as a key residue for discriminating against incorrect nucleotide incorporation. This residue also plays an important role in the stabilization of the active position of the DNA even when the DNA is misaligned and poised for a deletion error.**Projected dynamics from molecular dynamics simulations**

Rodolphe Vuilleumier (École Normale Supérieure)

It is often desirable to reduce the description of an atomic system to the dynamics of only a few relevant, usually, slow variables. Projection methods offer a rigourous framework to perform such reduction of variables. The main outcome of the method is the definition of a memory or friction kernel for the reduced dynamics. The memory kernel is equal to the time correlation of a so-called random force acting on the relevant variables. The evolution of the random force is not governed by the natural microscopic dynamics but by a projected dynamics. We have tried to illustrate this projected dynamics through the design of a method to directly compute the projected correlation functions from Molecular Dynamics simulations. Not only did this allow us to compute the memory kernel for the self-diffusion of Lennard-Jones particles but il also allowed for the decomposition of the memory kernel into short range and long range interactions contributions. Finally, long time behavior of the projected dynamics is investigated.**Molecular modelling with help from invariant theory and**

computer algebra

Bastiaan Braams (Emory University)

Invariant theory concerns an algebra K[V]^{G}: the polynomials on a

vector space V over a field K that are invariant under the action

of a group G that is represented on V. In the case of a finite

group acting on a finite-dimensional vector space over a field of

characteristic zero, and in other cases not of present concern, this

algebra is finitely generated in the Cohen-Macaulay form of a

finite-dimensional free module over a polynomial ring. Generators of

that ring (primary invariants) and a basis for the module (secondary

invariants) may be found by computer algebra. Molecular modelling

encompasses many things: molecular dynamics for the study of reaction

and isomerization processes, diffusion Monte Carlo for ground state

properties, path-integral Monte Carlo for thermal properties, and

direct diagonalization of a configuration-interaction matrix for

calculation of a ro-vibrational spectrum. A key tool in molecular

modelling for any specific system is an analytical, fitted potential

energy surface: the potential energy of the system as a function of

the spatial configuration of nuclei, as is obtained from first

principles by solution of the electronic Schroedinger equation. In

the work to be described here molecular modelling meets invariant

theory and computer algebra in the construction of potential energy

surfaces. A polynomial model in suitable variables is employed and

the model is explicitly invariant under the full molecular permutation

symmetry group. The MAGMA computer algebra system is employed to

obtain the generators. Using such a representation we are able to

construct quite routinely highly accurate potential energy surfaces

for systems of N=7 or more atoms in full (3N-6) dimensionality,

and with use of a many-body expansion also for larger systems such as

water clusters.**Optimal fuzzy aggregation of Markov chains**

Christof Schütte (Freie Universität Berlin)

Joint work with Marco Sarich (Freie Universität Berlin).

We map a discrete-time Markov Chain onto another Markov Chain describing transitions between some clusters only.

Every such aggregated Markov chain and affiliation function can be lifted again onto the full state space to define the so-called lifted transition matrix.

The optimal aggregated Markov chain and affiliation function can then be determined by minimizing some appropriately defined distance between the lifted transition matrix and the transition matrix of the original chain.**Hard-core colloids forming stable crystals:**

Clusters - columns - lamellae - compact

Gerhard Kahl (Technische Universität Wien)

Joint work with Gernot J. Pauschenwein.

The success of experiments to design colloidal particles that interact

like classical hard spheres reintroduced lively work on systems

interacting via a hard core and various attached potential tails. We

investigated the equilibrium crystal structures at zero temperature of

hard--core systems interacting additionally either via soft shoulder

(polymer--grafted colloids) or Yukawa interactions (equally charged

colloids in salty solvent). Our investigations are based on

optimisation strategies that use ideas of genetic algorithms. The

problem of excluding a priori structures with overlapping cores

from search space was solved by introducing a particular

parametrisation of all crystal lattices. This parametrisation

drastically improved the performance of the genetic algorithm.

The application of this approach to the soft shoulder potential

revealed a large number of equilibrium structures in dependence of

ambient pressure, ranging from clusters over columns and lamellae to

finally compact structures. The close--packed structure with the

lowest energy per particle can, in dependence of the shoulder width,

be one with a different stacking of hexagonal layers than both fcc

(ABC) or hcp (AB), as the genetic algorithm revealed and was proven

theoretically. For hard core Yukawa systems the genetic algorithm

gives, as expected, fcc or bcc depending on pressure and interaction

range over the vast majority of parameter space. However our

investigation gives evidence that the phase transformation from bcc to

fcc at high pressure is happening through a continuous Bain

transformation, giving rise to a small regime of centered tetragonal

symmetry.**The interplay of AAA+ molecular machines and sliding**

clamps at the DNA replication fork

Ivaylo Ivanov (University of California, San Diego)

Replication of chromosomal DNA is accomplished by a dynamic protein assembly termed the replisome. Within the replisome, the function of replicative DNA polymerases is to rapidly and faithfully duplicate the cell’s genetic material prior to cell division. During replication proliferating cell nuclear antigen (PCNA, sliding clamp) serves as an accessory protein whose role is to topologically tether DNA polymerase to DNA. PCNA also acts as a scaffold in the recruitment of proteins involved in cell-cycle control and DNA repair. Mounting recent experimental evidence has pointed to the involvement of sliding clamps in almost every aspect of DNA metabolism. Yet many mechanistic details of how these fascinating proteins are loaded onto DNA and function within the machinery of the replisome have remained unknown.

To perform its vital functions the clamp has to be opened and resealed at DNA primer-template junctions by the action of a clamp loader ATPase – replication factor C (RFC). Recent computational work on the RFC/PCNA complex will be presented. It established that upon clamp opening the complex undergoes a large conformational rearrangement, leading to the formation of an extended interface between the surface of the sliding clamp and RFC. An interface complementary to ring-open PCNA transforms the free energy landscape underlying the closed- to open state transition, effectively trapping PCNA in an open conformation. Thus, careful comparison of free energy profiles for clamp opening in the presence and absence of RFC has allowed us to substantiate the role of the clamp loader in the initial stage of the clamp-loading cycle.**Flexible-boundary QM/MM: Partial charge transfer between the QM and MM subsystems**

Hai Lin (University of Colorado Denver)

A prominent limitation of the commonly-used QM/MM methods is that no partial transfer is allowed between the QM and MM subsystems. A challenging example is the Eigen cation (Fig. 1), where one models the inner moiety H3O+ by QM and the surrounding three H2O molecules by MM. Both mutual polarization and partial charge transfer are expected between the QM and MM subsystems. This work aims to go beyond the above limit by incorporating partial charge transfer between the QM and MM subsystems, which (we hope) could lead to more accurate description for the QM/MM electrostatic interactions.**Membrane channels: Diffusion in confined geometries and**

entropic barriers

Juan Latorre (Freie Universität Berlin)

In this work we present a mathematical approach to the study of diffusing particles confined to narrow geometries, such as water and ion channels in cell membranes. In this model, a strong potential (such as an electric field) drives the particle to remain close to the center of the channel, so that the dynamics in the direction parallel to the channel may be described by an averaged equation with an effective Fixman potential driving the motion of the particle. The Fixman potential depends on the particular geometry of the channel, accounting for entropic barriers (bottlenecks) whose effective heights are proportional to temperature. We compare transport properties such as flux rate and effective diffusivity when the typical barrier is either entropic or energetic.**Statistical behavior of the self-guided dynamics**

algorithms

Daniel Smith (University of Pittsburgh)

The self-guided dynamics algorithms are a pair of techniques to

increase the speed of sampling from the possible conformations for a

macromolecule. Wu and Wang (1998), and later Wu and Brooks (2003),

proposed a numerical scheme that introduced a biasing term based on a

running average of past states of the system into the equations of

motion to increase the rate of barrier-crossings. In the present work,

an analytical form for the guiding force is derived from the numerical

methods. That analytical form is used to study the sampling properties

of the two algorithms. It is shown that, up to a separability

assumption, the systems do not sample from the Boltzmann distribution,

and the magnitudes of the error are estimated. Finally, a new

thermostat for the self-guided algorithms that conserves the Boltzmann

distribution is proposed.