title: Accurate detection of protein:ligand binding sites using molecular dynamics simulations.
abstract: Accurate prediction of location of cavities and surface grooves in proteins is important, as these are potential sites for ligand binding. Several currently available programs for cavity detection are unable to detect cavities near the surface or surface grooves. In the present study, an optimized molecular dynamics based procedure is described for detection and quantification of interior cavities as well as surface pockets. This is based on the observation that the mobility of water in such pockets is significantly lower than that of bulk water. The algorithm efficiently detects surface grooves that are sites of protein-ligand and protein-protein interaction. The algorithm was also used to substantially improve the performance of an automated docking procedure for docking monomers of nonobligate protein-protein complexes. In addition, it was applied to predict key residues involved in the binding of the E. coli toxin CcdB with its inhibitor. Predictions were subsequently validated by mutagenesis experiments.
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Akshay
authors.initials: A
authors.lastname: Bhinge
authors.forename: Purbani
authors.initials: P
authors.lastname: Chakrabarti
authors.forename: Kavitha
authors.initials: K
authors.lastname: Uthanumallian
authors.forename: Kanika
authors.initials: K
authors.lastname: Bajaj
authors.forename: Kausik
authors.initials: K
authors.lastname: Chakraborty
authors.forename: Raghavan
authors.initials: R
authors.lastname: Varadarajan
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D016296:Mutagenesis; D011485:Protein Binding
chemical_list: D029968:Escherichia coli Proteins; D008024:Ligands