These authors contributed equally to this work.
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CovalentDock: Automated covalent docking with parameterized covalent linkage energy estimation and molecular geometry constraints
Article first published online: 4 OCT 2012
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Computational Chemistry
Volume 34, Issue 4, pages 326–336, 5 February 2013
How to Cite
Ouyang, X., Zhou, S., Su, C. T. T., Ge, Z., Li, R. and Kwoh, C. K. (2013), CovalentDock: Automated covalent docking with parameterized covalent linkage energy estimation and molecular geometry constraints. J. Comput. Chem., 34: 326–336. doi: 10.1002/jcc.23136
- Issue published online: 13 JAN 2013
- Article first published online: 4 OCT 2012
- Manuscript Accepted: 5 SEP 2012
- Manuscript Revised: 6 AUG 2012
- Manuscript Received: 7 MAR 2012
- Singapore MOE AcRF. Grant Number: MOE2008-T2-1-074
- National Natural Science Foundation of China. Grant Number: 21172011
- covalent docking;
- covalent drug;
- molecular docking;
- virtual screening;
- computer-aided drug design
Covalent linkage formation is a very important mechanism for many covalent drugs to work. However, partly due to the limitations of proper computational tools for covalent docking, most covalent drugs are not discovered systematically. In this article, we present a new covalent docking package, the CovalentDock, built on the top of the source code of Autodock. We developed an empirical model of free energy change estimation for covalent linkage formation, which is compatible with existing scoring functions used in docking, while handling the molecular geometry constrains of the covalent linkage with special atom types and directional grid maps. Integrated preparation scripts are also written for the automation of the whole covalent docking workflow. The result tested on existing crystal structures with covalent linkage shows that CovalentDock can reproduce the native covalent complexes with significant improved accuracy when compared with the default covalent docking method in Autodock. Experiments also suggest that CovalentDock is capable of covalent virtual screening with satisfactory enrichment performance. In addition, the investigation on the results also shows that the chirality and target selectivity along with the molecular geometry constrains are well preserved by CovalentDock, showing great capability of this method in the application for covalent drug discovery. © 2012 Wiley Periodicals, Inc.