Fuzzy Drug Targets: Disordered Proteins in the Drug-Discovery Realm
Suman Saurabh, Karthik Nadendla, Shubh Sanket Purohit, Ponnurengam Malliappan Sivakumar, Sibel Çetinel
Abstract
. Consequently, they are involved in various disease pathways and are plausible drug targets. Unlike folded proteins, that have a defined structure and well carved out drug-binding pockets that can guide lead molecule selection, the disordered proteins require alternative drug-development methodologies that are based on an acceptable picture of their conformational ensemble. In this review, we discuss various experimental and computational techniques that contribute toward understanding IDP "structure" and describe representative pursuances toward IDP-targeting drug development. We also discuss ideas on developing rational drug design protocols targeting IDPs.