title: Computational titration analysis of a multiprotic HIV-1 protease-ligand complex.
abstract: A new computational method for analyzing the protonation states of protein-ligand complexes with multiple ionizable groups is applied to the structurally characterized complex between the peptide Glu-Asp-Leu and HIV-1 protease. This complex has eight ionizable groups at the active site: four from the ligand and four Asp residues on the protein. Correlation, with an error of ca. 0.6 kcal mol-1, is made between the calculated titration curve and the experimental titration curve. The analysis suggests that between four and five of the eight ionizable groups are protonated at the pH of crystallization.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Parma, 43100, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Spyrakis
authors.forename: Micaela
authors.initials: M
authors.lastname: Fornabaio
authors.forename: Pietro
authors.initials: P
authors.lastname: Cozzini
authors.forename: Andrea
authors.initials: A
authors.lastname: Mozzarelli
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Abraham
authors.forename: Glen E
authors.initials: GE
authors.lastname: Kellogg
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D016333:HIV Protease / Q000737:chemistry* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D012996:Solutions; D013816:Thermodynamics; D017186:Titrimetry
chemical_list: D017320:HIV Protease Inhibitors; D008024:Ligands; D009842:Oligopeptides; D012996:Solutions; D016333:HIV Protease