Pharmacophore model based on IN-DKA complexes and refined according to an effective binding mode
HIV-1 integrase (IN) is an essential enzyme for HIV-1 replication, so it can also be regarded as an attractive target for finding new drugs, but still no drug of anti-IN come into market. Up to now, most of anti-HIV drugs can make the virus drug resistant. New drug discovery is important to Highly Active Anti-Retroviral Therapy (HAART). Pharmacophore is a powerful tool for new drug discovery and design. At present, there are some studies on DKA Pharmacophores, but all have shortcomings. This study derived Pharmacophore based on five IN-DKA complexes, not only used X-ray structure. Then the mode was refined by an effective binding model generated by comparing drug resistance mutant complexes with wild-type IN complex. It made the pharmacophore more reasonable and effective. The refined model can be used to identify novel inhibitors.
integrase pharmacophore DKAs HIV drug resistance mutants
Xiao-Yi Zhang Bin Liu Cun-Xin Wang
College of Life Science and Bioengineering,Beijing University of Technology,Beijing China,100022
国际会议
The 5th International Forum on Post-genome Technologies(5IFPT)(第五届国际后基因组生命科学技术学术论坛)
苏州
英文
2007-09-10（万方平台首次上网日期，不代表论文的发表时间）