title: Prediction of the binding mode of N2-phenylguanine derivative inhibitors to herpes simplex virus type 1 thymidine kinase.
abstract: The probable binding mode of the herpes simplex virus thymidine kinase (HSV1 TK) N2-[substituted]-phenylguanine inhibitors is proposed. A computational experiment was designed to check some qualitative binding parameters and to calculate the interaction binding energies of alternative binding modes of N2-phenylguanines. The known binding modes of the HSV1 TK natural substrate deoxythymidine and one of its competitive inhibitors ganciclovir were used as templates. Both the qualitative and quantitative parts of the computational experiment indicated that the N2-phenylguanine derivatives bind to the HSV1 TK active site in the deoxythymidine-like binding mode. An experimental observation that N2-phenylguanosine derivatives are not phosphorylated during the interaction with the HSV1 TK gives support to the proposed binding mode.
authors.affiliation: Departamento de Física, Universidade Federal do Espírito Santo, Campus de Goiabeiras, Vitória, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Gaudio
authors.forename: Y
authors.initials: Y
authors.lastname: Takahata
authors.forename: W G
authors.initials: WG
authors.lastname: Richards
mesh_terms: D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001665:Binding Sites; D001667:Binding, Competitive; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D015774:Ganciclovir / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D008958:Models, Molecular; D010766:Phosphorylation; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013816:Thermodynamics; D013936:Thymidine / Q000737:chemistry / Q000378:metabolism; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; C088966:N(2)-phenylguanine; D006147:Guanine; D013937:Thymidine Kinase; D015774:Ganciclovir; D013936:Thymidine