Implementation of the Hungarian algorithm to account for ligand symmetry and similarity in structure-based design.
J Chem Inf Model
; 54(2): 518-29, 2014 Feb 24.
Article
en En
| MEDLINE
| ID: mdl-24410429
ABSTRACT
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 source code, is available to registered users of DOCK6 ( http//dock.compbio.ucsf.edu ).
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Diseño de Fármacos
/
Simulación del Acoplamiento Molecular
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Chem Inf Model
Asunto de la revista:
INFORMATICA MEDICA
/
QUIMICA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos