Investigation on the Effect of Key Water Molecules on Docking Performance in CSARdock Exercise

• Published in: Journal of chemical information and modeling Vol. 53; no. 8; pp. 1880 - 1892
• Main Authors: Kumar, Ashutosh, Zhang, Kam Y. J
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 26.08.2013
• Subjects: Applied sciences; Benchmarks; Biological and medical sciences; Computer science; control theory; systems; Computer systems performance. Reliability; Databases, Pharmaceutical; Exact sciences and technology; Exercise; Fundamental and applied biological sciences. Psychology; General pharmacology; Interactions. Associations; Intermolecular phenomena; Medical sciences; Molecular biophysics; Molecular Docking Simulation - methods; Molecules; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; Protein Conformation; Proteins; Proteins - chemistry; Proteins - metabolism; Simulation; Software; Structure-Activity Relationship; Thermodynamics; Water; Water; Blind; Ligand binding; Molecular interaction; Binding site; Experimental study; Binding protein; Molecular physics; Scoring credit; Biopolymer; Program proof; Program test; Chemical system; Comparative study
• ISSN: 1549-9596; 1549-960X
• DOI: 10.1021/ci400052w

Water molecules are routinely included in molecular docking methods and protocols because of their important role in mediating ligand protein interactions. However, it is still unclear that the inclusion of explicit water molecules improves docking accuracy. To explore the effect of including key water molecules on docking accuracy and performance, we participated in the CSARdock 2011 benchmark exercise. This exercise provides a valuable opportunity for researchers to test their docking programs, methods, and protocols in a blind testing environment. The benchmark exercise and its analysis presented in this paper showed that the performance of current docking programs can be improved by incorporating carefully selected water molecules. Our study showed that water mapping calculations can be used to select key water molecules from experimentally identified water positions for molecular dockings. We have observed that inclusion of all binding site water molecules led to reduced performance and erroneous results. Moreover, an overall improvement in binding pose prediction was achieved when computationally selected water molecules are included during docking simulations. The improvement in the docking performance by including water molecules also depends on protein system, chemical class of ligand, docking method, and scoring function.