title: A density functional study of the hydrogen-bond network within the HIV-1 protease catalytic site cleft.
abstract: The relative energy between two different protonation sites of the Asp25' catalytic site residue is computed and analyzed for various HIV-1 Protease/inhibitor complexes and compared to the wild-type structure. By comparing calculations of negatively charged fragments of gradually increasing size up to 105 atoms we show that correct modeling of the HIV-1 Protease active site requires much larger models than the commonly used acetic acid/acetate moieties. The energy difference between the two proposed protonation sites decreases as the size of the system increases and tends to converge only when the entire catalytic triad of both monomers is taken into account. The importance of the Gly27 backbone amine groups in the stabilization of the negative charge within the catalytic site cleft is revealed. Comparison of the wild-type structure with the structures from various Pr/drug complexes indicates that the HIV-1 protease has a particular catalytic site flexibility.
authors.affiliation: Centre de Recherche en Calcul Appliqué CERCA, 5160, boul Décarie, bureau 400, Montréal, Québec, H3X 2H9 Canada.
authors.forename: S
authors.initials: S
authors.lastname: Sirois
authors.forename: E I
authors.initials: EI
authors.lastname: Proynov
authors.forename: J-F
authors.initials: JF
authors.lastname: Truchon
authors.forename: C M
authors.initials: CM
authors.lastname: Tsoukas
authors.forename: D R
authors.initials: DR
authors.lastname: Salahub
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D020134:Catalytic Domain; D016333:HIV Protease / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D016333:HIV Protease