Premium
Selecting near‐native conformations in homology modeling: The role of molecular mechanics and solvation terms
Author(s) -
Janardhan Ajit,
Vajda Sandor
Publication year - 1998
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560070812
Subject(s) - solvation , molecular mechanics , implicit solvation , chemistry , statistical mechanics , side chain , closure (psychology) , computational chemistry , molecular dynamics , statistical physics , chemical physics , physics , molecule , polymer , organic chemistry , economics , market economy
A free energy function, combining molecular mechanics energy with empirical solvation and entropic terms, is used for ranking near‐native conformations that occur in the conformational search steps of homology modeling, i.e., side‐chain search and loop closure calculations. Correlations between the free energy and RMS deviation from the X‐ray structure are established. It is shown that generally both molecular mechanics and solvation/entropic terms should be included in the potential. The identification of near‐native backbone conformations is accomplished primarily by the molecular mechanics term that becomes the dominant contribution to the free energy if the backbone is even slightly strained, as frequently occurs in loop closure calculations. Both terms become equally important if a sufficiently accurate backbone conformation is found. Finally, the selection of the best side‐chain positions for a fixed backbone is almost completely governed by the solvation term. The discriminatory power of the combined potential is demonstrated by evaluating the free energies of protein models submitted to the first meeting on Critical Assessment of techniques for protein Structure Prediction (CASP1), and comparing them to the free energies of the native conformations.