TY - JOUR T1 - Design of Multi-Specificity in Protein Interfaces A1 - Humphris, Elisabeth L A1 - Kortemme, Tanja Y1 - 2007/08/24 N2 -
Computational methods have recently led to remarkable successes in the design of molecules with novel functions. These approaches offer great promise for creating highly selective molecules to accurately control biological processes. However, to reach these goals modeling procedures are needed that are able to define the optimal “fitness” of a protein to function correctly within complex biological networks and in the context of many possible interaction partners. To make progress toward these goals, we describe a computational design procedure that predicts protein sequences optimized to bind not only to a single protein but also to a set of target interaction partners. Application of the method to characterize “hub” proteins in cellular interaction networks gives insights into the mechanisms nature has used to tune protein surfaces to recognize multiple correct partner proteins. Our study also provides a starting point to engineer designer molecules that could modulate or replace naturally occurring protein interaction networks to combat misregulation in disease or to build new sets of protein interactions for synthetic biology.