Implementationof the Hungarian Algorithm to Accountfor Ligand Symmetry and Similarity in Structure-Based Design

摘要

False negative docking outcomes for highly symmetric molecules are a barrier to the accurate evaluation of docking programs, scoring functions, and protocols. This work describes an implementation of a symmetry-corrected root-mean-square deviation (RMSD) method into the program DOCK based on the Hungarian algorithm for solving the minimum assignment problem, which dynamically assigns atom correspondence in molecules with symmetry. The algorithm adds only a trivial amount of computation time to the RMSD calculations and is shown to increase the reported overall docking success rate by approximately 5% when tested over 1043 receptor–ligand systems. For some families of protein systems the results are even more dramatic, with success rate increases up to 16.7%. Several additional applications of the method are also presented including as a pairwise similarity metric to compare molecules during de novo design, as a scoring function to rank-order virtual screening results, and for the analysis of trajectories from molecular dynamics simulation. The new method, including sourcecode, is available to registered users of DOCK6 ().