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

该项目旨在生成能够选择性结合心肌肌球蛋白特定构象的药物样化合物。这将首先通过使用分子动力学、分子对接和虚拟筛选等计算技术来确定一系列对肌球蛋白功能具有不同预测影响的小分子。具有最佳亲和力和选择性的候选化合物将在心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发展。

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.