title: Computational binding studies of human pp60c-src SH2 domain with a series of nonpeptide, phosphophenyl-containing ligands.
abstract: Monte Carlo/free energy perturbation (MC/FEP) simulations were performed on a series of nonpeptide ligands of the human pp60c-src SH2 domain in order to calculate relative free energies of binding for each compound and to understand the structural requirements for high affinity binding. The amido compound, exhibiting the highest experimental affinity, takes advantage of an interaction with a previously unobserved structural water.
authors.affiliation: Department of Chemistry, Yale University, New Haven, CT 06500-8107, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Price
authors.forename: W L
authors.initials: WL
authors.lastname: Jorgensen
mesh_terms: D001665:Binding Sites; D006801:Humans; D008024:Ligands; D008956:Models, Chemical; D008968:Molecular Conformation; D009010:Monte Carlo Method; D010755:Organophosphates / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D018909:src Homology Domains
chemical_list: D008024:Ligands; D010755:Organophosphates; C074782:phenylphosphate; D016392:Proto-Oncogene Proteins pp60(c-src)