In silico modeling of IDPs: challenges and limitations in uncovering the physical rules that underlie protein assembly and folding.

Intrinsically Disordered Proteins (IDPs) are functional proteins that exhibit conformational heterogeneity due to a lack of an ordered 3D folded structure. Despite this proclivity, IDPs play critical roles in many important biological processes such as: cellular-division, regulation of protein complex assembly, signal transduction, and protein phosphorylation to name a few. The simulation of IDPs seeks to uncover the rules and grammar that govern protein assembly, aggregation, folding and misfolding but is beset by limitations in four major areas: physics, chemistry, computing, and theory. This talk will discuss several aspects surrounding those challenges from a force-field development context.