Improving conformational searches by geometric screening.
BACKGROUND
Conformational searches in molecular docking are a time-consuming process with wide range of applications. Favorable conformations of the ligands that successfully bind with receptors are sought to form stable ligand-receptor complexes. Usually a large number of conformations are generated and their binding energies are examined. We propose adding a geometric screening phase before an energy minimization procedure so that only conformations that geometrically fit in the binding site will be prompted for energy calculation.


RESULTS
Geometric screening can drastically reduce the number of conformations to be examined from millions (or higher) to thousands (or lower). The method can also handle cases when there are more variables than geometric constraints. An early-stage implementation is able to finish the geometric filtering of conformations for molecules with up to nine variables in 1 min. To the best of our knowledge, this is the first time such results are reported deterministically.


BACKGROUND
mzhang@mdanderson.org.
Zhang
Ming
M
Department of Biostatistics and Applied Mathematics, The University of Texas M.D. Anderson Cancer Center Houston, TX 77030, USA. mzhang@mdanderson.org
White
R Allen
RA
Wang
Liqun
L
Goldman
Ronald
R
Kavraki
Lydia
L
Hassett
Brendan
B
D000465:Algorithms; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000032:analysis / Q000737:chemistry*; D013329:Structure-Activity Relationship
D011506:Proteins