Evaluating the Effects of Cutoffs and Treatment of Long-range Electrostatics in Protein Folding Simulations

The use of molecular dynamics simulations to provide atomic-level descriptions of biological processes tends to be computationally demanding, and a number of approximations are thus commonly employed to improve computational efficiency. In the past, the effect of these approximations on macromolecul...

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Bibliographic Details
Published in:PloS one Vol. 7; no. 6; p. e39918
Main Authors: Piana, Stefano, Lindorff-Larsen, Kresten, Dirks, Robert M., Salmon, John K., Dror, Ron O., Shaw, David E.
Format: Journal Article
Language:English
Published: United States Public Library of Science 29.06.2012
Public Library of Science (PLoS)
Subjects:
Accuracy
Algorithms
Analysis
Approximation
Atomic structure
Biological activity
Biology
Chemical reactions
Chemistry
Computer applications
Computer Simulation
Computing time
Electrostatic properties
Electrostatics
Folding
Fourier transforms
Free energy
Macromolecules
Methods
Microfilament Proteins - chemistry
Molecular dynamics
Physics
Protein Folding
Protein Structure, Secondary
Quantitative analysis
Quantitative research
Simulation
Stability analysis
Static Electricity
Structural stability
Testing equipment
Thermodynamics
Van der Waals forces
New York
United States > US
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary:The use of molecular dynamics simulations to provide atomic-level descriptions of biological processes tends to be computationally demanding, and a number of approximations are thus commonly employed to improve computational efficiency. In the past, the effect of these approximations on macromolecular structure and stability has been evaluated mostly through quantitative studies of small-molecule systems or qualitative observations of short-timescale simulations of biological macromolecules. Here we present a quantitative evaluation of two commonly employed approximations, using a test system that has been the subject of a number of previous protein folding studies--the villin headpiece. In particular, we examined the effect of (i) the use of a cutoff-based force-shifting technique rather than an Ewald summation for the treatment of electrostatic interactions, and (ii) the length of the cutoff used to determine how many pairwise interactions are included in the calculation of both electrostatic and van der Waals forces. Our results show that the free energy of folding is relatively insensitive to the choice of cutoff beyond 9 Å, and to whether an Ewald method is used to account for long-range electrostatic interactions. In contrast, we find that the structural properties of the unfolded state depend more strongly on the two approximations examined here.
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Conceived and designed the experiments: SP KL-L RMD DES. Performed the experiments: SP KL-L RMD. Analyzed the data: SP KL-L RMD. Contributed reagents/materials/analysis tools: JKS. Wrote the paper: SP KL-L RMD ROD DES.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0039918