|  | | | | Detecting and understanding combinatorial mutation patterns responsible for HIV drug resistance | | | Autor(es): | ZHANG, Jing (*) et al.
(*) Department of Statistics, Harvard University, Science Center, Cambridge, MA/USA | | Instituição: | National Academy of Sciences | | País: | Washington/DC, USA | | Publicação/Editora: | PNAS, vol. 107, nº 4, p. 1321–1326 | | Data da publicação: | 26/0/2010 | | Número de Páginas: | 6 | | Veiculação no PEC: | 04/03/2010 17h15 | | Resumo: | | We propose a systematic approach for a better understanding of how HIV viruses employ various combinations of mutations to resist drug treatments, which is critical to developing new drugs and optimizing the use of existing drugs. By probabilistically modeling mutations in the HIV-1 protease or reverse transcriptase (RT) isolated from drug-treated patients, we present a statistical procedure that first detects mutation combinations associated with drug resistance and then infers detailed interaction structures of these mutations. The molecular basis of our statistical predictions is further studied by using molecular dynamics simulations and free energy calculations. We have demonstrated the usefulness of this systematic procedure on three HIV drugs, (Indinavir, Zidovudine, and Nevirapine), discovered unique interaction features between viral mutations induced by these drugs, and revealed the structural basis of such interactions. | | Arquivo para Download: | | PEC-SBI_HIVAids_Detecting and understanding combinatorial mutation.pdf | | Links Relacionados: | | http://www.pnas.org/content/107/4/1321.full.pdf |
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