MOLECULAR DYNAMICS SIMULATIONS OF THE ACTIVATION OF THE ADENOVIRUS PROTEINASE B

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 本项目的目的是通过分子动力学模拟来确定腺病毒蛋白水解酶(AVP)被其11个氨基酸的肽辅因子(PVIc)激活的结构基础。失活酶(AVP)和激活酶(AVP-pVIc)的晶体结构是已知的。对这些结构的分析表明，当pVIc与AVP结合时，激活可能通过一系列连续的结构变化的信号转导途径发生。分子动力学模拟将被用来确定结构变化的顺序。未来，分子动力学模拟的结果将用于基于结构的药物设计，以获得抗病毒药物。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The objective of this project is to determine the structural basis for the activation of the adenovirus proteinase (AVP) by its 11-amino-acid peptide cofactor (pVIc) using molecular dynamics simulations. Crystal structures of the inactive enzyme (AVP) and of the activated enzyme (AVP-pVIc) are known. Analysis of these structures indicates that upon the binding of pVIc to AVP activation may occur via a signal transduction pathway involving a series of contiguous structural changes. Molecular dynamics simulations will be used to determine the sequence of structural changes. In the future, the results of the molecular dynamics simulations will be used with structure-based drug design to obtain anti-viral agents.