The Development of Computer-Aided Molecular Modelling and Drug Design Techniques for Flexible Enzyme Targets - New Anti-HIV Agents

在许多情况下，蛋白质在小分子结合时的动态运动对于蛋白质的功能或作用于蛋白质的药物的功能是至关重要的。目前的方法在计算机辅助设计的小分子结合蛋白质不考虑这种蛋白质的灵活性充分。本项目打算为此目的开发分子动力学模拟技术，最初使用HIV逆转录酶作为靶蛋白。然而，所制定的方法将普遍适用。该项目还旨在设计、合成和测试专门针对艾滋病毒耐药性的新型药物。

The dynamic motion of proteins upon binding of small molecules is crucial in many cases for the function of the protein or for the function of drugs acting upon the protein. Current methods in computer-aided design of small molecules binding to proteins do not take this protein flexibility fully into account. This project intends to develop molecular dynamics simulation techniques for this purpose, initially using the HIV reverse transcriptase enzyme as the target protein. The methods developed will, however, be universally applicable. The project further aims to design, synthesise and test novel medicinal agents specifically against drug resistance in HIV.