Applying advanced computer methods to understand genetic disorders

The Rett syndrome is a progressive neurodevelopmental disorder and one of the most common causes of mental retardation in females. Because males have a different chromosome combination from females, most males with Rett syndrome die before birth or in early infancy. It was not until 1999 that it was discovered that the Rett syndrome is caused by mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2). MeCP2 belongs to a class of proteins called Intrinsically Disordered Proteins (IDPs). In contrast with globular proteins, IDPs do not have a well-defined secondary or tertiary structure and can adopt a wide range of conformations. This makes their structural characterization a challenge. We have studied MeCP2 and determined that there currently is no single method that can do it. However, combination of ABF and our metadynamics-based methods appears to offer the possibility to resolve the problem. If successful, this study would lead to a scientific breakthrough, helping us to identify the effects of reported mutations and potentially bring us one step closer to develop a treatment that may improve the lives of those diagnosed with Rett syndrome.

Faculty Supervisor:

Mikko Karttunen

Student:

Partner:

Institut de Biologie Physico-Chimique

Discipline:

Physics

Sector:

Life Sciences (not health); Pharmaceuticals; Biotechnology

University:

Western University

Program: