Previous work has shown that cancer-associated proteins are rich in intrinsic disorder Given that many of the current techniques used in drug discovery are confounded by disordered protein, new approaches are required The overall goal is to enable the biotechnology community to gain understanding and work effectively with disordered proteins through development of customized research contracts The tools proposed here are critically important for the success of these contracts The proposed tools to accelerate protein structure determination are based on two important observations disordered proteins fail to yield crystal structures, and a large fraction of solved structures are fragments of longer gene products The goal is to develop two predictors that will find 1) the likelihood of obtaining a protein crystal and 2) the regions of a protein most likely to be structured These tools will rely on previously developed predictors of natural disordered regions and other sequence determinants These tools will provide the biotechnology and pharmaceutical industries with useful analysis for breaking bottlenecks in 3-D structure determination and improving protein target prioritization Since many cancer-associated proteins contain significant disordered regions, these products have potential for improving human health.
| Cheng, Yugong; LeGall, Tanguy; Oldfield, Christopher J et al. (2006) Rational drug design via intrinsically disordered protein. Trends Biotechnol 24:435-42 |
