EnzyDock: Protein-Ligand Docking of Multiple Reactive States along a Reaction Coordinate in Enzymes

Journal of Chemical Theory and Computation
Susanta DasDan Thomas Major

Abstract

Enzymes play a pivotal role in all biological systems. These biomachines are the most effective catalysts known, dramatically enhancing the rate of reactions by more than 10 orders of magnitude relative to the uncatalyzed reactions in solution. Predicting the correct, mechanistically appropriate binding modes for substrate and product, as well as all reaction intermediates and transition states, along a reaction pathway is immensely challenging and remains an unsolved problem. In the present work, we developed an effective methodology for identifying probable binding modes of multiple ligand states along a reaction coordinate in an enzyme active site. The program is called EnzyDock and is a CHARMM-based multistate consensus docking program that includes a series of protocols to predict the chemically relevant orientation of substrate, reaction intermediates, transition states, product, and inhibitors. EnzyDock is based on simulated annealing molecular dynamics and Monte Carlo sampling and allows ligand, as well as enzyme side-chain and backbone flexibility. The program can employ many user-defined constraints and restraints and classical force field potentials, as well as a range of hybrid quantum mechanics-molecular mechanics ...Continue Reading

References

May 25, 1977·Journal of Molecular Biology·F C BernsteinM Tasumi
Sep 5, 1991·Journal of Molecular Biology·B K Shoichet, I D Kuntz
Jan 1, 1990·Proteins·D S Goodsell, A J Olson
Oct 25, 1982·Journal of Molecular Biology·I D KuntzT E Ferrin
Jul 1, 1995·The Plant Cell·D J McGarvey, R Croteau
Dec 1, 1995·Current Opinion in Biotechnology·G Jones, P Willett
Aug 1, 1996·Journal of Computer-aided Molecular Design·G M MorrisA J Olson
Apr 4, 1997·Journal of Molecular Biology·G JonesR Taylor
Apr 30, 1999·Science·J BrookeG Aeppli
Jun 14, 2002·Journal of Medicinal Chemistry·Alexey V Ishchenko, Eugene I Shakhnovich
Jun 19, 2002·Protein Science : a Publication of the Protein Society·Csaba Hetényi, David van der Spoel
Sep 25, 2002·Proceedings of the National Academy of Sciences of the United States of America·Alessandro Laio, Michele Parrinello
Nov 15, 2002·Proceedings of the National Academy of Sciences of the United States of America·Douglas A WhittingtonDavid W Christianson
Feb 8, 2003·Annual Review of Biophysics and Biomolecular Structure·Natasja Brooijmans, Irwin D Kuntz
Aug 12, 2003·Proteins·Marcel L VerdonkRichard D Taylor
Sep 10, 2003·Journal of Computational Chemistry·Wonpil ImCharles L Brooks
Jan 30, 2004·Journal of the American Chemical Society·Kaushik Raha, Kenneth M Merz
Mar 11, 2004·Journal of Computational Chemistry·Ricardo L ManceraNikolay P Todorov
Mar 19, 2004·Journal of Medicinal Chemistry·Richard A FriesnerPeter S Shenkin
Mar 19, 2004·Journal of Medicinal Chemistry·Thomas A HalgrenJay L Banks
Mar 20, 2004·Science·William L Jorgensen
Nov 3, 2004·Nature Reviews. Drug Discovery·Douglas B KitchenJürgen Bajorath
Feb 25, 2005·Bioorganic & Medicinal Chemistry·Youngchool ChoeCharles S Craik
Apr 21, 2005·Journal of Computational Chemistry·Art E ChoRichard Friesner
Sep 30, 2005·Journal of Medicinal Chemistry·Marcel L VerdonkRobin Taylor
Dec 3, 2005·Journal of Computational Chemistry·Jie HuAaron R Dinner
Feb 1, 2006·Proceedings of the National Academy of Sciences of the United States of America·Alejandro BuschiazzoPaola Minoprio
Feb 3, 2006·Journal of Medicinal Chemistry·Jay P PowersZhulun Wang
Jul 25, 2006·Proteins·Sérgio Filipe SousaMaria João Ramos
Aug 10, 2006·Chemical Reviews·Arieh WarshelMats H M Olsson
Sep 7, 2006·Journal of Computational Chemistry·Stefan Grimme
Mar 6, 2007·Nature Chemical Biology·Jimmy A BlairKevan M Shokat
Mar 6, 2007·Journal of Computational Chemistry·H Lee WoodcockBernard R Brooks
May 13, 1983·Science·S KirkpatrickM P Vecchi
Nov 27, 2007·British Journal of Pharmacology·N MoitessierC R Corbeil
Feb 28, 2008·Current Opinion in Structural Biology·Maxim Totrov, Ruben Abagyan
Aug 30, 2008·Journal of Computational Chemistry·Victor M Anisimov, Vladislav L Bugaenko
Nov 7, 2008·The Journal of Physical Chemistry. a·Christopher J R IllingworthChristopher A Reynolds
Dec 2, 2008·Journal of Molecular Biology·Ian W Davis, David Baker
Mar 25, 2009·Journal of Chemical Information and Modeling·Pedro FongRichard A Bryce
Apr 18, 2009·Journal of Computational Chemistry·Art E Cho, David Rinaldo
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson

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Citations

Nov 2, 2019·Beilstein Journal of Organic Chemistry·Ronja DrillerBernhard Loll
Jul 18, 2020·Current Opinion in Biotechnology·Keren RazDan Thomas Major
Oct 21, 2021·Chembiochem : a European Journal of Chemical Biology·Nicole G H Leferink, Nigel S Scrutton

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