PREDICTION OF THE BINDING MODE OF N-2-PHENYLGUANINE DERIVATIVE INHIBITORS TO HERPES-SIMPLEX VIRUS TYPE-1 THYMIDINE KINASE

The probable binding mode of the herpes simplex virus thymidine kinase (HSV1 TK) N-2-[substituted]-phenylguanine inhibitors is proposed. A c omputational experiment was designed to check some qualitative binding parameters and to calculate the interaction binding energies of alter native binding modes of N-2-phenylguanines, The known binding modes of the HSV1 TK natural substrate deoxythymidine and one of its competiti ve inhibitors ganciclovir were used as templates. Both the qualitative and quantitative parts of the computational experiment indicated that the N-2-phenylguanine derivatives bind to the HSV1 TK active site in the deoxythymidine-like binding mode. An experimental observation that N-2-phenylguanosine derivatives are not phosphorylated during the int eraction with the HSV1 TK gives support to the proposed binding mode.