Bellucci Luca, Angeli Lucilla, Tafi Andrea, Radi Marco, Botta Maurizio
Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena , Via Aldo Moro 2, 53100 Siena, Italy.
J Chem Inf Model. 2013 Dec 23;53(12):3117-22. doi: 10.1021/ci400414s. Epub 2013 Nov 25.
Targeted molecular dynamics (TMD) simulations allowed for identifying the chemical/structural features of the nucleotide-competitive HIV-1 inhibitor DAVP-1, which is responsible for the disruption of the T-shape motif between Try183 and Trp229 of the reverse transcriptase (RT). DAVP-1 promoted the opening of a connection "gate" between allosteric and catalytic sites of HIV-1 RT, thus explaining its peculiar mechanism of action and providing useful insights to develop novel nucleotide-competitive RT inhibitors.
靶向分子动力学（TMD）模拟有助于确定核苷酸竞争性HIV-1抑制剂DAVP-1的化学/结构特征，该抑制剂导致逆转录酶（RT）的Try183和Trp229之间的T形基序被破坏。DAVP-1促进了HIV-1 RT变构位点和催化位点之间连接“门”的打开，从而解释了其独特的作用机制，并为开发新型核苷酸竞争性RT抑制剂提供了有用的见解。
