Evaluating the effects of cutoffs and treatment of long-range electrostatics in protein folding simulations
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Evaluating the effects of cutoffs and treatment of long-range electrostatics in protein folding simulations. / Piana, Stefano; Lindorff-Larsen, Kresten; Dirks, Robert M; Salmon, John K; Dror, Ron O; Shaw, David E.
I: P L o S One, Bind 7, Nr. 6, 2012.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Evaluating the effects of cutoffs and treatment of long-range electrostatics in protein folding simulations
AU - Piana, Stefano
AU - Lindorff-Larsen, Kresten
AU - Dirks, Robert M
AU - Salmon, John K
AU - Dror, Ron O
AU - Shaw, David E
N1 - e39918
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pone.0039918
DO - 10.1371/journal.pone.0039918
M3 - Journal article
C2 - 22768169
VL - 7
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 6
ER -
ID: 40287134