Targeting cardiac myosin: a structure-based approach to design conformation-selective modulators

该项目旨在产生能够选择性结合心肌肌球蛋白特定构象的药物样化合物。这将首先使用计算技术，如分子动力学，分子对接和虚拟筛选，以确定一系列的小分子与不同的预测影响肌球蛋白功能。具有最佳亲和性和选择性的候选化合物将在心肌肌球蛋白和心肌细胞上进行体外运动试验。这项研究的结果将直接影响治疗心力衰竭和遗传性心肌病等心血管疾病的药物的开发。

This project aims to generate drug-like compounds able to selectively bind specific conformations of cardiac myosin. This will be done by first using computational techniques such as Molecular Dynamics, Molecular Docking and virtual screening to identify a range of small molecules with different predicted effects on myosin function. The candidate compounds with best affinity and selectivity will be then tested on cardiac myosin and cardiomyocytes with in vitro motility assays. Results of this research will directly impact the development of drugs to treat cardiovascular diseases such as heart failure and inherited cardiomyopathies.