Three parallel algorithms for classical molecular dynamics are presented. The first assigns each processor a fixed subset of atoms; the second assigns each a fixed subset of inter-atomic forces to compute; the third assigns each a fixed spatial region. The algorithms are suitable for molecular dynamics models which can be difficult to parallelize efficiently—those with short-range forces where the neighbors of each atom change rapidly. They can be implemented on any distributed-memory parallel machine which allows for message-passing of data between independently executing processors. The algorithms are tested on a standard Lennard-Jones benchmark problem for system sizes ranging from 500 to 100,000,000 atoms on several parallel supercomputers--the nCUBE 2, Intel iPSC/860 and Paragon, and Cray T3D. Comparing the results to the fastest reported vectorized Cray Y-MP and C90 algorithm shows that the current generation of parallel machines is competitive with conventional vector supercomputers even for small problems. For large problems, the spatial algorithm achieves parallel efficiencies of 90% and a 1840-node Intel Paragon performs up to 165 faster than a single Cray C9O processor. Trade-offs between the three algorithms and guidelines for adapting them to more complex molecular dynamics simulations are also discussed.

Fast parallel algorithms for short-range molecular dynamics

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

The previously developed particle mesh Ewald method is reformulated in terms of efficient B‐spline interpolation of the structure factors This reformulation allows a natural extension of the method to potentials of the form 1/rp with p≥1 Furthermore, efficient calculation of the virial tensor follows Use of B‐splines in place of Lagrange interpolation leads to analytic gradients as well as a significant improvement in the accuracy We demonstrate that arbitrary accuracy can be achieved, independent of system size N, at a cost that scales as N log(N) For biomolecular systems with many thousands of atoms this method permits the use of Ewald summation at a computational cost comparable to that of a simple truncation method of 10 A or less

A smooth particle mesh Ewald method

6.2.2. Definition of Effective Properties 3064 6.3. Response Properties to Magnetic Fields 3066 6.3.1. Nuclear Shielding 3066 6.3.2. Indirect Spin−Spin Coupling 3067 6.3.3. EPR Parameters 3068 6.4. Properties of Chiral Systems 3069 6.4.1. Electronic Circular Dichroism (ECD) 3069 6.4.2. Optical Rotation (OR) 3069 6.4.3. VCD and VROA 3070 7. Continuum and Discrete Models 3071 7.1. Continuum Methods within MD and MC Simulations 3072

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Quantum mechanical continuum solvation models.

New protein parameters are reported for the all-atom empirical energy function in the CHARMM program. The parameter evaluation was based on a self-consistent approach designed to achieve a balance between the internal (bonding) and interaction (nonbonding) terms of the force field and among the solvent−solvent, solvent−solute, and solute−solute interactions. Optimization of the internal parameters used experimental gas-phase geometries, vibrational spectra, and torsional energy surfaces supplemented with ab initio results. The peptide backbone bonding parameters were optimized with respect to data for N-methylacetamide and the alanine dipeptide. The interaction parameters, particularly the atomic charges, were determined by fitting ab initio interaction energies and geometries of complexes between water and model compounds that represented the backbone and the various side chains. In addition, dipole moments, experimental heats and free energies of vaporization, solvation and sublimation, molecular volume...

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All-atom empirical potential for molecular modeling and dynamics studies of proteins.

An expression for the atomic forces in simulations using the charge-on-spring (COS) polarizable model is rederived. In previous implementations of COS-based models, contributions arising from the dependence of the induced dipoles (i.e., the positions of the charges-on-spring) on the coordinates of the other sites in the system were not taken into account. However, from calculations on gas-phase dimers we found a significant contribution of these terms. Errors in the forces when neglecting these contributions in condensed-phase calculations can be significantly reduced by choosing an appropriately large value for the size of the charge-on-spring.

On the Calculation of Atomic Forces in Classical Simulation Using the Charge-on-Spring Method To Explicitly Treat Electronic Polarization.

Publisher Summary This chapter illustrates the current knowledge on the unfolded state of peptides. Currently, the characterization of the populated microscopic states of a peptide is possible only by simulation methods. The focus is on molecular dynamics simulations of spontaneous (i.e., lacking biasing potentials or directed-sampling algorithms) and reversible folding of peptides in solution (i.e., with explicit solvent molecules), since the results from this type of studies are the least dependent on the methodology. A full characterization of the unfolded state becomes as essential as the determination of the folded conformation in two scenarios. The first is in the study of the physical, chemical, and biological properties of peptides. The folded conformation of a peptide is, in general, only marginally more stable than the lowest-free-energy unfolded conformation. As a result, any macroscopic observable of a peptide is weighted with both the folded and the unfolded states. Interpreting such observables in terms of the folded conformation only is therefore not correct. The second scenario is related to the study of peptide and protein folding. The description of equilibrium requires knowledge about each of the states involved. Therefore, it is fundamental to describe not only the folded state but also the unfolded state accurately in order to draw conclusions on the nature and mechanisms of peptide and protein folding.

Unfolded state of peptides.

The influence of valine side chains on the folding/unfolding equilibrium and, in particular, on the 314-helical propensity of β3-peptides were investigated by means of molecular-dynamics (MD) simulation. To that end, the valine side chains in two different β3-peptides were substituted by leucine side chains. The resulting four peptides, of which three have never been synthesized, were simulated for 150 to 200 ns at 298 and 340 K, starting from a fully extended conformation. The simulation trajectories obtained were compared with respect to structural preferences and folding behavior. All four peptides showed a similar folding behavior and were found to predominantly adopt 314-helical conformations, irrespective of the presence of valine side chains. No other well-defined conformation was observed at significant population in any of the simulations. Our results imply that β3-peptides show a structural preference for 314-helices independent of the branching nature of the side chains, in contrast to what has been previously proposed on the basis of circular-dichroism (CD) measurements.

Do valine side chains have an influence on the folding behavior of β-substituted β-peptides?

The three-metal-containing β domain of rat liver metallothionein-2 in aqueous solution was simulated with different metal contents. The Cd3, the CdZn2, and the Zn3 variant were investigated using a conventional molecular dynamics simulation, as well as a simulation with a semi-empirical quantum-chemical description (MNDO and MNDO/d) of the metal core embedded in a classical environment. For the purely classical simulations, the standard GROMOS96 force-field parameters were used, and parameters were estimated for cadmium. The results of both kinds of simulations were compared to each other and to the corresponding experimental X-ray crystallographic and NMR solution data. The purely classical simulations were found to produce a too compact metal cluster with partially incorrect geometries, which affected the enfolding protein backbone structure. The inclusion of MNDO/d for the treatment of the metal cluster improved the results to give correct cluster geometries and an overall protein structure in agreement with the experiment. The metal cluster and the cysteine residues bound to it are structurally stable, while the irregular polypeptide backbone loops between the cysteines exhibit a considerable flexibility. MNDO without extension to d orbitals failed to maintain the structure of the metal core. Proteins 2000;41:299–315. © 2000 Wiley-Liss, Inc.

Wilfred F. van Gunsteren

Papers

On the Calculation of Atomic Forces in Classical Simulation Using the Charge-on-Spring Method To Explicitly Treat Electronic Polarization.

Unfolded state of peptides.

Do valine side chains have an influence on the folding behavior of β-substituted β-peptides?

Molecular-dynamics simulation of the β domain of metallothionein with a semi-empirical treatment of the metal core

Are NMR‐Derived Model Structures for β‐Peptides Representative for the Ensemble of Structures Adopted in Solution?