Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: " In-Silico docking of HIV-1 integrase inhibitors reveals a novel drug type acting on an enzyme/DNA reaction intermediate. | Retrovirology BioMed Central Research In-Silico docking of HIV-1 integrase inhibitors reveals a novel drug type acting on an enzyme DNA reaction intermediate Andrea Savarino Open Access Address Department of Infectious Parasitic and Immune-mediated Diseases Istituto Superiore di Sanità Viale Regina Elena 299 00161 Rome Italy Email Andrea Savarino - asavarino@ Corresponding author Published 20 March 2007 Received 12 February 2007 Accepted 20 March 2007 Retrovirology 2007 4 21 doi l 742-4690-4-21 This article is available from http content 4 1 21 2007 Savarino licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http licenses by which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Abstract Background HIV-1 integrase IN is an emerging drug target as IN strand transfer inhibitors INSTIs are proving potent antiretroviral agents in clinical trials. One credible theory sees INSTIs as docking at the cellular acceptor DNA-binding site after IN forms a transitional complex with viral donor DNA. However mapping of the DNA and INSTI binding sites within the IN catalytic core domain CCD has been uncertain. Methods Structural superimpositions were conducted using the SWISS PDB and Cn3D free software. Docking simulations of INSTIs were run by a widely validated genetic algorithm GOLD . Results Structural superimpositions suggested that a two-metal model for HIV-l IN CCD in complex with small molecule 1- 5-chloroindol-3-yl -3- tetrazoyl -1 3-propandione-ene 5CITEP could be used as a surrogate for an IN viral DNA complex because it allowed replication of contacts documented biochemically in viral DNA IN complexes or displayed by a crystal structure of the IN-related enzyme Tn5 .
