为了获得p53突变体的稳定剂,依次利用利宾斯基五原则,通过2次分子对接和全原子分子动力学(MD)模拟从Drug Bank 4.0数据库中筛选获得了潜在的稳定剂他克林.利用MD模拟进一步验证他克林和目标蛋白质之间的亲和作用.结果表明,他克林能够紧...为了获得p53突变体的稳定剂,依次利用利宾斯基五原则,通过2次分子对接和全原子分子动力学(MD)模拟从Drug Bank 4.0数据库中筛选获得了潜在的稳定剂他克林.利用MD模拟进一步验证他克林和目标蛋白质之间的亲和作用.结果表明,他克林能够紧密结合到Y220C突变所形成的疏水空腔之中;他克林和目标蛋白质之间的主要作用力为疏水和静电相互作用,其中疏水相互作用占主导地位.此外,他克林分别与目标蛋白质的残基Leu145,Val147和Asp228形成3个氢键.基于MD模拟轨迹分析了他克林与p53CY220C的结合过程.由硫黄素T荧光光谱进一步证明他克林能够提高p53C-Y220C突变体的稳定性.展开更多
HIV- 1 RT is an important target for the treatment of AIDS. There are two major classes of antiviral agents that inhibit HIV- 1 RT have been identified, nucleoside RT inhibitors （NRTIs） and non-nucleoside RT inhibit...HIV- 1 RT is an important target for the treatment of AIDS. There are two major classes of antiviral agents that inhibit HIV- 1 RT have been identified, nucleoside RT inhibitors （NRTIs） and non-nucleoside RT inhibitors （NNRTIs）. In this report, a noval class of non-nucleoside compound with potential RT inhibitory activity were found from the traditional Chinese medicines database （TCMD） using a combination of virtual screening, docking, molecular dynamic simulations, where results were ranked by scoring function of the docking tool. The result indicates that M4753 （a compound derived from TCMD） has not only the lowest bonding energy but also the best match in geometric conformation with the forthcoming NNRTIs. Accordingly M4753 might possibly become a promising lead compound of NNRTIs for AIDS therapy.展开更多
文摘为了获得p53突变体的稳定剂,依次利用利宾斯基五原则,通过2次分子对接和全原子分子动力学(MD)模拟从Drug Bank 4.0数据库中筛选获得了潜在的稳定剂他克林.利用MD模拟进一步验证他克林和目标蛋白质之间的亲和作用.结果表明,他克林能够紧密结合到Y220C突变所形成的疏水空腔之中;他克林和目标蛋白质之间的主要作用力为疏水和静电相互作用,其中疏水相互作用占主导地位.此外,他克林分别与目标蛋白质的残基Leu145,Val147和Asp228形成3个氢键.基于MD模拟轨迹分析了他克林与p53CY220C的结合过程.由硫黄素T荧光光谱进一步证明他克林能够提高p53C-Y220C突变体的稳定性.
基金supported by the grants from Chinese National Science Foundation(No.30472166)the Tianjin Commission of Sciences and Technology under the Contract(No.06YFGZSH07000)
文摘HIV- 1 RT is an important target for the treatment of AIDS. There are two major classes of antiviral agents that inhibit HIV- 1 RT have been identified, nucleoside RT inhibitors （NRTIs） and non-nucleoside RT inhibitors （NNRTIs）. In this report, a noval class of non-nucleoside compound with potential RT inhibitory activity were found from the traditional Chinese medicines database （TCMD） using a combination of virtual screening, docking, molecular dynamic simulations, where results were ranked by scoring function of the docking tool. The result indicates that M4753 （a compound derived from TCMD） has not only the lowest bonding energy but also the best match in geometric conformation with the forthcoming NNRTIs. Accordingly M4753 might possibly become a promising lead compound of NNRTIs for AIDS therapy.
