Project title: Rational Design of Selective Modulators of Skeletal Myosin
Summary: Due to developing research, there is now a better understanding of the pathophysiology of muscular disorders such as nemaline myopathy. Notably, a link between these disorders and altered myosin binding to actin molecules has been discovered. Myosin has therefore received a growing interest as a possible drug target.
The primary aim of the project is to discover small molecule modulators which selectively bind skeletal muscle myosin II over other myosin classes, and develop these to increase their selectivity and function. Computational techniques such as homology modelling, virtual screening, compound docking and molecular dynamics will be conducted to build a model for skeletal muscle myosin, screen existing drug like compounds and determine their selectivity, affinity and binding conformation. To determine the molecular mode of action, the most promising modulators will be selected and tested in in vitro assays. This research will form the basis of future studies aimed at the optimisation of pharmacokinetic properties and the general development of therapies for muscular diseases.