Computational design of a leucine-rich repeat protein with a predefined geometry.

ABSTRACT: Structure-based protein design offers a possibility of optimizing the overall shape of engineered binding scaffolds to match their targets better. We developed a computational approach for the structure-based design of repeat proteins that allows for adjustment of geometrical features like length, curvature, and helical twist. By combining sequence optimization of existing repeats and de novo design of capping structures, we designed leucine-rich repeats (LRRs) from the ribonuclease inhibitor (RI) family that assemble into structures with a predefined geometry. The repeat proteins were built from self-compatible LRRs that are designed to interact to form highly curved and planar assemblies. We validated the geometrical design approach by engineering a ring structure constructed from 10 sel

SUBMITTER: Ramisch S 

PROVIDER: S-EPMC4273356 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature