Journal
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
Volume 22, Issue 5, Pages 405-413Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jmgm.2003.12.007
Keywords
softcore potential; potential of mean force; PMF; steric barriers; conformational sampling; loop prediction; molecular dynamics
Categories
Funding
- NIGMS NIH HHS [GM6167803, R01 GM061678, R01 GM061678-04] Funding Source: Medline
Ask authors/readers for more resources
In this work, we describe the development of softcore potential functions that permit occasional tunneling through the regions of conformational space during molecular dynamics (MD) simulations, which would otherwise be sterically prohibited. The modification consists of a truncation of the nonbonded interaction before the steeply repulsive region encountered at short interatomic distances. This modification affects both Lennard-Jones and Coulomb parts of the nonbonded potential. Critical to success is the choice of appropriate pairwise switching distances at which this modification should be made. In the present work, these are calculated based on potential of mean force functions extracted from model system molecular dynamics simulations. We believe that these functions describe the dynamic short-range interactions much better than mean force potentials derived from an ensemble of static structures (e.g. protein data bank (PDB)). Once a set of mean force potentials is obtained, a single empirical parameter, effective barrier height, is employed to determine switching distances for all pairwise atomic interactions. Changing this single parameter allows adjustment of the softness of the whole system. We tested the applicability of the new softcore potentials in a loop structure optimization study. The H I loop in the antibody 17/9 was selected,is our test case because substantial repacking of loop residues in the dense protein environment is necessary for successful relaxation of random initial conformations. Softcore simulations converted to correct loop conformations, in contrast to standard simulations which never sampled this structure even after 10 ns. The resulting root mean square deviation (RMSD) values (below 1.3 A for all heavy atoms of the loop) demonstrate the usefulness of the approach based on mean force derived softcore functions. (C) 2004 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available