Bioinformatics Advance Access originally published online on October 12, 2004
Bioinformatics 2005 21(5):624-630; doi:10.1093/bioinformatics/bti055
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Improving conformational searches by geometric screening
1 Department of Biostatistics and Applied Mathematics, The University of Texas M.D. Anderson Cancer Center Houston, TX 77030, USA
2 Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston Houston, TX 77225, USA
3 Department of Computer Science, Rice University Houston, TX 77251, USA
4 Department of Bioengineering, Rice University Houston, TX 77251, USA
5 Department of Mathematics, Rice University Houston, TX 77251, USA
6 Graudate Program in Structural and Computational Biology, Baylor College of Medicine Houston, TX 77030, USA
*To whom correspondence should be addressed.
Motivation: 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.
Contact: mzhang{at}mdanderson.org