Interactive molecular dynamics in virtual reality for accurate flexible protein-ligand docking

PloS One
Helen M DeeksDavid R Glowacki


Simulating drug binding and unbinding is a challenge, as the rugged energy landscapes that separate bound and unbound states require extensive sampling that consumes significant computational resources. Here, we describe the use of interactive molecular dynamics in virtual reality (iMD-VR) as an accurate low-cost strategy for flexible protein-ligand docking. We outline an experimental protocol which enables expert iMD-VR users to guide ligands into and out of the binding pockets of trypsin, neuraminidase, and HIV-1 protease, and recreate their respective crystallographic protein-ligand binding poses within 5-10 minutes. Following a brief training phase, our studies shown that iMD-VR novices were able to generate unbinding and rebinding pathways on similar timescales as iMD-VR experts, with the majority able to recover binding poses within 2.15 Å RMSD of the crystallographic binding pose. These results indicate that iMD-VR affords sufficient control for users to carry out the detailed atomic manipulations required to dock flexible ligands into dynamic enzyme active sites and recover crystallographic poses, offering an interesting new approach for simulating drug docking and generating binding hypotheses.


Jun 16, 1977·Nature·J A McCammonM Karplus
Jan 1, 1984·Progress in Biophysics and Molecular Biology·E N Baker, R E Hubbard
Feb 7, 1995·Biochemistry·J J PeronaR J Fletterick
Feb 1, 1994·Protein Science : a Publication of the Protein Society·M C SurlesF P Brooks
Apr 1, 1997·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·W E Hart, S Istrail
Jan 13, 2000·Protein Science : a Publication of the Protein Society·F PolticelliB Honig
Apr 25, 2002·Annual Review of Physical Chemistry·Peter G BolhuisPhillip L Geissler
Dec 19, 2002·Journal of Biomedicine & Biotechnology·Naem Shahrour
Aug 22, 2003·Organic & Biomolecular Chemistry·Ashraf Brik, Chi-Huey Wong
May 5, 2005·Proceedings of the National Academy of Sciences of the United States of America·M Karplus, J Kuriyan
Aug 3, 2005·Nature Reviews. Microbiology·Taisuke Horimoto, Yoshihiro Kawaoka
Jul 21, 2006·The Journal of Physical Chemistry. B·Weinan EEric Vanden-Eijnden
Dec 1, 2007·Nature Reviews. Drug Discovery·Mark von Itzstein
Jun 8, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ignasi BuchGianni De Fabritiis
Nov 18, 2009·Journal of Physics. Condensed Matter : an Institute of Physics Journal·Rosalind J AllenPieter Rein Ten Wolde
Jul 14, 2011·Nature Communications·Rommie E AmaroRobin M Bush
Feb 22, 2012·Journal of Computer-aided Molecular Design·Parimal Kar, Volker Knecht
May 17, 2012·Journal of Chemical Information and Modeling·Georgios LeonisManthos G Papadopoulos
Dec 21, 2013·Scientific Reports·Christopher J WoodsAdrian J Mulholland
Aug 12, 2014·European Journal of Medicinal Chemistry·Hongtao Zhao, Amedeo Caflisch
Sep 11, 2014·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Moritz P HaagMarkus Reiher
Oct 24, 2014·The Journal of Physical Chemistry. B·T Dwight McGeeAdrian E Roitberg
Nov 18, 2015·Journal of Chemical Theory and Computation·Nathan LuehrTodd J Martínez
May 13, 2014·Journal of Chemical Theory and Computation·S Doerr, G De Fabritiis
Nov 21, 2015·Journal of Chemical Theory and Computation·Maxwell I Zimmerman, Gregory R Bowman
Feb 14, 2016·Chemical Biology & Drug Design·Mukul MahantiPär Söderhjelm
Apr 16, 2016·Journal of Chemical Information and Modeling·Ali HosseiniVictor Guallar
May 10, 2016·Journal of Chemical Theory and Computation·Ivan TeoTony Lelièvre
May 17, 2017·Biophysics Reviews·Nataraj S PagadalaJack Tuszynski
Nov 18, 2017·Current Opinion in Structural Biology·Paweł Śledź, Amedeo Caflisch
Nov 23, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dario GioiaAndrea Cavalli
Apr 3, 2018·Biophysical Journal·Rommie E AmaroJeremy C Smith
Jul 3, 2018·Science Advances·Michael O'ConnorDavid R Glowacki

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