A Brownian dynamics treatment in torsional angle space was constructed for the simulation of conformational dynamics of macromolecules with fixed bond lengths and bond angles and with an arbitrary intramolecular potential energy function. The advantages of the torsional angle space treatment over similar treatments (Brownian dynamics or molecular dynamics) in atomic coordinate space are that the number of variables is reduced by roughly a factor of 10 and that the integration time step size is increased by three to four orders of magnitude. Consequently, the exploration of global conformational relaxation processes becomes computationally possible. The treatment is a general purpose one applicable to all macromolecular conformational relaxation processes (e.g., protein folding kinetics, drug/ligand docking on to target proteins, conformational multiple-minima problems, etc.). The torsional angle space Brownian dynamics treatment has been used to study the mechanism and kinetics of protein folding by using continuum rigid chain molecules (with unit bond lengths and tetrahedral bond angles). It is found that the torsional angle space approach is much faster and more reliable than similar approaches in atomic coordinate space. The simulation results also suggest that the short-ranged Lennard-Jones binary interactions alone are not sufficient to fold the chain molecules, and that hydrophobic collapse is essential for the folding processes. In our simplified protein folding model, the hydrophobic collapse is achieved by introducing global dipole interactions. The collapse of the chain molecule induced by dipole interactions significantly reduces the folding time. The chain collapse processes effectively bring the atoms into the (short) range of Lennard-Jones attractions, which then, in turn, are able to play their role in the folding processes; without such collapse the folding processes are highly frustrated.
| Chiang, Chi-Tung; Shores, Kevin S; Freindorf, Marek et al. (2008) Size-restricted proton transfer within toluene-methanol cluster ions. J Phys Chem A 112:11559-65 |
| Kazmierkiewicz, Rajmund; Liwo, Adam; Scheraga, Harold A (2003) Addition of side chains to a known backbone with defined side-chain centroids. Biophys Chem 100:261-80 |
| Kazmierkiewicz, Rajmund; Liwo, Adam; Scheraga, Harold A (2002) Energy-based reconstruction of a protein backbone from its alpha-carbon trace by a Monte-Carlo method. J Comput Chem 23:715-23 |
| Liwo, Adam; Arlukowicz, Piotr; Czaplewski, Cezary et al. (2002) A method for optimizing potential-energy functions by a hierarchical design of the potential-energy landscape: application to the UNRES force field. Proc Natl Acad Sci U S A 99:1937-42 |
| Scheraga, Harold A; Pillardy, Jaroslaw; Liwo, Adam et al. (2002) Evolution of physics-based methodology for exploring the conformational energy landscape of proteins. J Comput Chem 23:28-34 |
| Scheraga, Harold A; Vila, Jorge A; Ripoll, Daniel R (2002) Helix-coil transitions re-visited. Biophys Chem 101-102:255-65 |
| Pillardy, J; Arnautova, Y A; Czaplewski, C et al. (2001) Conformation-family Monte Carlo: a new method for crystal structure prediction. Proc Natl Acad Sci U S A 98:12351-6 |
| Vila, J A; Ripoll, D R; Scheraga, H A (2001) Influence of lysine content and pH on the stability of alanine-based copolypeptides. Biopolymers 58:235-46 |
| Pillardy, J; Czaplewski, C; Liwo, A et al. (2001) Recent improvements in prediction of protein structure by global optimization of a potential energy function. Proc Natl Acad Sci U S A 98:2329-33 |
| Czaplewski, C; Rodziewicz-Motowidlo, S; Liwo, A et al. (2000) Molecular simulation study of cooperativity in hydrophobic association. Protein Sci 9:1235-45 |
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