title: Analysis of factors influencing hydration site prediction based on molecular dynamics simulations.
abstract: Water contributes significantly to the binding of small molecules to proteins in biochemical systems. Molecular dynamics (MD) simulation based programs such as WaterMap and WATsite have been used to probe the locations and thermodynamic properties of hydration sites at the surface or in the binding site of proteins generating important information for structure-based drug design. However, questions associated with the influence of the simulation protocol on hydration site analysis remain. In this study, we use WATsite to investigate the influence of factors such as simulation length and variations in initial protein conformations on hydration site prediction. We find that 4 ns MD simulation is appropriate to obtain a reliable prediction of the locations and thermodynamic properties of hydration sites. In addition, hydration site prediction can be largely affected by the initial protein conformations used for MD simulations. Here, we provide a first quantification of this effect and further indicate that similar conformations of binding site residues (RMSD < 0.5 Å) are required to obtain consistent hydration site predictions.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University , 575 Stadium Mall Drive, West Lafayette, Indiana 47907, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Bingjie
authors.initials: B
authors.lastname: Hu
authors.forename: Markus A
authors.initials: MA
authors.lastname: Lill
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D005777:Geese / Q000378:metabolism; D056004:Molecular Dynamics Simulation / Q000706:statistics & numerical data*; D009113:Muramidase / Q000737:chemistry*; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000201:enzymology; D011487:Protein Conformation; D011734:Pyridoxaminephosphate Oxidase / Q000737:chemistry*; D013816:Thermodynamics; D013997:Time Factors; D014584:User-Computer Interface; D014867:Water / Q000737:chemistry*
chemical_list: D030161:Avian Proteins; D001426:Bacterial Proteins; D014867:Water; D011734:Pyridoxaminephosphate Oxidase; D009113:Muramidase