Protein-Folding Dynamics: Overview of Molecular Simulation Techniques
Harold A. Scheraga, Mey Khalili, Adam Liwo
2007
Annual review of physical chemistry (Print)
Molecular dynamics (MD) is an invaluable tool with which to study protein folding in silico. Although just a few years ago the dynamic behavior of a protein molecule could be simulated only in the neighborhood of the experimental conformation (or protein unfolding could be simulated at high temperature), the advent of distributed computing, new techniques such as replica-exchange MD, new approaches (based on, e.g., the stochastic difference equation), and physics-based reduced models of
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... now make it possible to study proteinfolding pathways from completely unfolded structures. In this review, we present algorithms for MD and their extensions and applications to protein-folding studies, using all-atom models with explicit and implicit solvent as well as reduced models of polypeptide chains. 57 Annu. Rev. Phys. Chem. 2007.58:57-83. Downloaded from arjournals.annualreviews.org by University of Virginia Libraries on 12/07/09. For personal use only. NMR: nuclear magnetic resonance MD: molecular dynamics 58 Scheraga · Khalili · Liwo Annu. Rev. Phys. Chem. 2007.58:57-83. Downloaded from arjournals.annualreviews.org by University of Virginia Libraries on 12/07/09. For personal use only. MC: Monte Carlo UNRES: united-residue interior is fluid-like in that the local atomic motions have a diffusional character. Researchers have applied this technique extensively in the refinement of X-ray and NMR structures, but because of the need to take small (femtosecond) time steps along the evolving trajectory to keep the numerical algorithm stable, it has not been successful in treating the real long-time folding of a globular protein, except for very small ones. However, many of the applications of MD of globular proteins have been made to the initial unfolding steps, followed by refolding. In applying the MD technique, one must consider numerous trajectories, rather than a single one, to cover the large multidimensional, conformational potential energy space and obtain proper statistical mechanical averages of the folding/unfolding properties. Since the first papers from the Karplus lab, numerous MD calculations have been carried out in the laboratories of Brooks (16), van Gunsteren (17) , Levitt (18), Jorgensen (19), Daggett (20, 21), Kollman (22), Pande (23), Berendsen (24), Baker (25), McCammon (26) , and others. This review is concerned with recent theoretical developments in protein-folding dynamics. Several reviews (20, 27, 28) have discussed earlier work in this field. The discussion here focuses on techniques to solve the classical equations of motion, using both an all-atom approach and an approach based on simplified models of the polypeptide chain, and to assess how far the field has progressed to be able to compute complete folding trajectories, as well as the final, native structure, based on physical principles (i.e., the interatomic potential energy and Newtonian mechanics). www.annualreviews.org • Protein-Folding Dynamics 59 Annu. Rev. Phys. Chem. 2007.58:57-83. Downloaded from arjournals.annualreviews.org by University of Virginia Libraries on 12/07/09. For personal use only. NVE: constant number of particles, volume, and energy ensemble NVT: constant number of particles, volume, and temperature ensemble NPT: constant number of particles, pressure, and temperature ensemble CHARMM: Chemistry at Harvard Molecular Mechanics AMBER: assisted model building with energy refinement GROMOS: Groningen molecular simulation CVFF: consistent valence force field enables one to increase the timescale further because of averaging out fast motions that are not present at the coarse-grained level (37, 40). 62 Scheraga · Khalili · Liwo Annu. Rev. Phys. Chem. 2007.58:57-83. Downloaded from arjournals.annualreviews.org by University of Virginia Libraries on 12/07/09. For personal use only.
doi:10.1146/annurev.physchem.58.032806.104614
pmid:17034338
fatcat:btpvknk56bas5mmz4uisurvhly