QM/QM docking method based on the variational finite localized molecular orbital approximation

Victor M. Anisimov, Vladislav L. Bugaenko

Research output: Contribution to journalArticlepeer-review


We present a derivation of the semiempirical variational finite localized molecular orbital (VFL) approximation, which was introduced by Anikin et al. (J Chem Phys 2004, 121, 1266). On the basis of VFL approximation, we developed the novel semiempirical (quantum mechanical) QM/QM method in which a part of the system, including the iigand and protein active site, are treated self-consistently, while the protein bulk is considered as carrying a frozen electronic density matrix. The developed method is applied toward the QM docking study for the p56 LCK SH2 domain. The virtual search has predicted 10 most potent inhibitors by searching through the database of 200,000 empirically docked poses of 20,000 drug-like molecules. Energy score calculation of each complex roughly consisting of 1700 atoms took 14,54 s of single-CPU time at the NDDO AMl level. The entire computation performed on a 32-CPU cluster would be accomplished in 1 day. Flexible ligand QM docking studies, performed on a subset of 10,000 poses, required 153.03 s of single-CPU time per complex. The entire calculation performed on the 32-CPU cluster would be finished in half-day.

Original languageEnglish (US)
Pages (from-to)784-798
Number of pages15
JournalJournal of Computational Chemistry
Issue number5
StatePublished - Apr 15 2009
Externally publishedYes


  • Docking
  • LocalSCF
  • P56 LCK tyrosine kinase
  • QM method
  • SH2 domain
  • Semiempirical method
  • Variational finite LMO approximation

ASJC Scopus subject areas

  • General Chemistry
  • Computational Mathematics


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