Long molecular dynamics simulations

How well has Dill s prediction held up In 2000, the first ever microsecond-long molecular dynamics simulation of protein folding was reported. It required 750,000 node hours (equal to the product of the number of hours times the number of processors) of computer time on a Cray T3 supercomputer. According to Dill s prediction, this length of simulation was not to be expected until around 2010. However, as noted above, Dill s analysis does not take into account large-scale parallelization—which, unless the computation is communications-limited, will effectively increase the speed of a computation in proportion to the number of processors available. 

RIS theory provides a relatively simle formalism for the evaluation of the persistence vector, a, for a chain that can be represented by a repeating sequence of independent virtual bonds such as polybenzobisoxazole (PBOI and polybenzobisthiazole IPBT). The present study combines RIS theory with long molecular dynamics simulations for small fragments in order to evaluate the limiting length of a for very stiff chains. The approach can be applied to other stiff chain polymers. 

Piana, S., J. L. Klepeis, and D. E. Shaw, Assessing the accuracy of physical models used in protein-folding simulations quantitative assessment from long molecular dynamics simulations. Curr. Opin. Struct. Biol, 2014. 24 98-105. 10.1016/j.sbi.201312.066. 

Sufficiently long molecular dynamics simulations can in principle provide complementary information to the CPMG dispersion experiments. Xue et al investigated this idea by analyzing a millisecond-long MD trajectory for the protein BPTI, obtained by Shaw et al They simulated the time dependence of amide N chemical shifts and used the data to predict outcome of N relaxation dispersion experiments. The results were found to confirm the experimental work. 

O. Chara, J. R. Grigera, and A. N. McCarthy,/. Biol. Phys., 33, 515 (2007). Studying the Unfolding Kinetics of Proteins Under Pressure Using Long Molecular Dynamics Simulation Runs. 

Since the development of grazing incidence x-ray diffraction, much of the convincing evidence for long-range positional order in layers has come from this technique. Structural relaxations from distorted hexagonal structure toward a relaxed array have been seen in heneicosanol [215]. Rice and co-workers combine grazing incidence x-ray diffraction with molecular dynamics simulations to understand several ordering transitions [178,215-219]. 

Tasaki, K., McDonald, S., Brady, J.W. Observations concerning the treatment of long range interactions in molecular dynamics simulations. J. Comput. Chem. 14 (1993) 278-284. 

Belhadj,M., Alper, H.A., Levy, R.M. Molecular dynamics simulations of wa ter with Ewald summation for the long-range electrostatic interactions. Chem. Phys. Lett. 179 (1991) 13-20. 

Helmut Grubmuller, Helmut Heller, Andreas Windemuth, and Klaus Schulten. Generalized Verlet algorithm for efficient molecular dynamics simulations with long-range interactions. Mol. Sim., 6 121-142, 1991. 

Grubmiiller, H., Heller, H., Windemuth, A., Schulten, K. Generalized Verlet Algorithm for Efficient Molecular Dynamics Simulations with Long-range Interactions. Molecular Simulation 6 (1991) 121-142... 

One drawback to a molecular dynamics simulation is that the trajectory length calculated in a reasonable time is several orders of magnitude shorter than any chemical process and most physical processes, which occur in nanoseconds or longer. This allows yon to study properties that change w ithin shorter time periods (such as energy finctnations and atomic positions), but not long-term processes like protein folding. 

Successful molecular dynamics simulations should have a fairly stable trajectory. Instability and lack of ec uilibratioii can result from a large time step, treatment of long-range cutoffs, or unrealistic coiiplin g to a temperature bath. ... 

Monte Carlo simulations require less computer time to execute each iteration than a molecular dynamics simulation on the same system. However, Monte Carlo simulations are more limited in that they cannot yield time-dependent information, such as diffusion coefficients or viscosity. As with molecular dynamics, constant NVT simulations are most common, but constant NPT simulations are possible using a coordinate scaling step. Calculations that are not constant N can be constructed by including probabilities for particle creation and annihilation. These calculations present technical difficulties due to having very low probabilities for creation and annihilation, thus requiring very large collections of molecules and long simulation times. 

A variety of techniques have been introduced to increase the time step in molecular dynamics simulations in an attempt to surmount the strict time step limits in MD simulations so that long time scale simulations can be routinely undertaken. One such technique is to solve the equations of motion in the internal degree of freedom, so that bond stretching and angle bending can be treated as rigid. This technique is discussed in Chapter 6 of this book. Herein, a brief overview is presented of two approaches, constrained dynamics and multiple time step dynamics. 

In a different context, conformational analysis is essential for the analysis of molecular dynamics simulations. As discussed in Chapter 3, the direct output of a molecular dynamics simulation is a set of confonnations ( snapshots ) that were saved along the trajectory. These conformations are subsequently analyzed in order to extract information about the system. However, if, during a long simulation, the molecule moves from one... 

The relative intensities of the bands in the transmission and RAIR spectra were used to determine the orientation of the long axis of the 4-MPP molecules with respect to the normal to the gold surface. It was found that this tilt angle was about 21°, a value that was similar to that obtained from molecular dynamics simulations [11]. 

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