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

Journal of Computational Chemistry
V M Anisimov, Vladislav L Bugaenko

Abstract

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 ligand 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 AM1 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.

References

Mar 24, 1999·Archives of Biochemistry and Biophysics·J M TrevillyanS W Djurić
Nov 20, 2002·The Journal of Pharmacology and Experimental Therapeutics·Stephen Rapecki, Rodger Allen
May 31, 2003·Nature Reviews. Drug Discovery·Josef S Smolen, Günter Steiner
Jul 21, 2004·The Journal of Chemical Physics·N A AnikinA M Andreyev
Jan 26, 2005·Journal of Chemical Information and Modeling·John J Irwin, Brian K Shoichet
Apr 21, 2005·Journal of Computational Chemistry·Art E ChoRichard Friesner
Jul 16, 2005·Journal of Computational Chemistry·R VillarV Martínez-Merino
Sep 14, 2006·Chemical Reviews·Andrea CavalliMaurizio Recanatini
Jun 30, 2007·Journal of Molecular Biology·David L MobleyKen A Dill
Mar 19, 2008·Journal of the American Chemical Society·Kwangho NamDarrin M York
Aug 30, 2008·Journal of Chemical Theory and Computation·Andrew M Wollacott, Kenneth M Merz
Nov 1, 2006·Journal of Chemical Theory and Computation·Victor M AnisimovVladimir V Bobrikov

❮ Previous
Next ❯

Citations

Mar 2, 2011·Journal of Molecular Recognition : JMR·Elizabeth YurievPaul A Ramsland
Apr 15, 2016·Chemical Reviews·Ulf Ryde, Pär Söderhjelm
Dec 17, 2016·Journal of Chemical Information and Modeling·Prasad ChaskarUte F Röhrig
May 10, 2012·Journal of Computational Chemistry·Jens Antony, Stefan Grimme
Aug 7, 2019·Journal of Chemical Theory and Computation·Susanta DasDan T Major

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.