An affinity-based scoring scheme for predicting DNA-binding activities of modularly assembled zinc-finger proteins.

ABSTRACT: Zinc-finger proteins (ZFPs) have long been recognized for their potential to manipulate genetic information because they can be engineered to bind novel DNA targets. Individual zinc-finger domains (ZFDs) bind specific DNA triplet sequences; their apparent modularity has led some groups to propose methods that allow virtually any desired DNA motif to be targeted in vitro. In practice, however, ZFPs engineered using this 'modular assembly' approach do not always function well in vivo. Here we report a modular assembly scoring strategy that both identifies combinations of modules least likely to function efficiently in vivo and provides accurate estimates of their relative binding affinities in vitro. Predicted binding affinities for 53 'three-finger' ZFPs, computed based on energy contributi

SUBMITTER: Sander JD 

PROVIDER: S-EPMC2632909 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature