Paper Info
Title
Application of torsion angle molecular dynamics for efficient sampling of protein conformations.
Abstract
We investigate the application of torsion angle molecular dynamics (TAMD) to augment conformational sampling of peptides and proteins. Interesting conformational changes in proteins mainly involve torsional degrees of freedom. Carrying out molecular dynamics in torsion space does not only explicitly sample the most relevant degrees of freedom, but also allows larger integration time steps with elimination of the bond and angle degrees of freedom. However, the covalent geometry needs to be fixed during internal coordinate dynamics, which can introduce severe distortions to the underlying potential surface in the extensively parameterized modern Cartesian-based protein force fields. A "projection" approach (Katritch et al. J Comput Chem 2003, 24, 254-265) is extended to construct an accurate internal coordinate force field (ICFF) from a source Cartesian force field. Torsion crossterm corrections constructed from local molecular fragments, together with softened van der Waals and electrostatic interactions, are used to recover the potential surface and incorporate implicit bond and angle flexibility. MD simulations of dipeptide models demonstrate that full flexibility in both the backbone phi/psi and side chain X-1 angles are virtually restored. The efficacy of TAMD in enhancing conformational sampling is then further examined by folding simulations of small peptides and refinement experiments of protein NMR structures. The results show that an increase of several fold in conformational sampling efficiency can be reliably achieved. The current study also reveals some complicated intrinsic properties of internal coordinate dynamics, beyond energy conservation, that can limit the maximum size of the integration time step and thus the achievable gain in sampling efficiency. (c) 2005 Wiley Periodicals, Inc.
Year
DOI
Venue
2005
10.1002/jcc.20293
JOURNAL OF COMPUTATIONAL CHEMISTRY
Keywords
Field
DocType
force field,generalized Born,implicit solvent,internal coordinate,NMR refinement,replica exchange,structure prediction
Electrostatics,Force field (physics),Torsion (mechanics),Computational chemistry,Chemistry,van der Waals force,Sampling (statistics),Molecular dynamics,Dihedral angle,Cartesian coordinate system
Journal
Volume
Issue
ISSN
26
15
0192-8651
Citations 
PageRank 
References 
14
1.34
6
Authors
3
Name
Order
Citations
PageRank
Jianhan Chen1366.06
Wonpil Im216317.39
Charles L. Brooks III31198126.06