TY - JOUR
T1 - Assessing energy functions for flexible docking
JF - Journal of Computational Chemistry
Y1 - 1999
A1 - Michal Vieth
A1 - Jonathan D. Hirst
A1 - Andrzej Koliński
A1 - Charles L. Brooks III
KW - docking
KW - dynamics
KW - energy functions
KW - Molecular
KW - scoring functions
KW - simulated annealing
AB - A good docking algorithm requires an energy function that is selective, in that it clearly differentiates correctly docked structures from misdocked ones, and that is efficient, meaning that a correctly docked structure can be identified quickly. We assess the selectivity and efficiency of a broad spectrum of energy functions, derived from systematic modifications of the CHARMM param19/toph19 energy function. In particular, we examine the effects of the dielectric constant, the solvation model, the scaling of surface charges, reduction of van der Waals repulsion, and nonbonded cutoffs. Based on an assessment of the energy functions for the docking of five different ligand–receptor complexes, we find that selective energy functions include a variety of distance-dependent dielectric models together with truncation of the nonbonded interactions at 8 Å. We evaluate the docking efficiency, the mean number of docked structures per unit of time, of the more selective energy functions, using a simulated annealing molecular dynamics protocol. The largest improvements in efficiency come from a reduction of van der Waals repulsion and a reduction of surface charges. We note that the most selective potential is quite inefficient, although a hierarchical approach can be employed to take advantage of both selective and efficient energy functions.
VL - 19
UR - http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1096-987X(19981115)19:14%3C1612::AID-JCC7%3E3.0.CO;2-M/abstract
IS - 14
ER -