In Silico Study Of Nonspecific DNA-protein Encounter Complexes

Abstract

In search of its specific targets, a DNA-binding protein associates with nonspecific DNA and subsequently diffuses along the DNA. Structural characterization of the nonspecific DNA-protein encounter complexes is of great interest. Due to weak interactions between the protein and nonspecific DNA, however, such characterization is experimentally challenging. Here, we describe the first comprehensive computational study on the encounter complexes of 44 specific DNA-binding proteins with nonspecific canonical B-DNA. In the analysis of these encounter complex models, we found that the recognition sites for specific DNA are usually favorable interaction sites for the nonspecific DNA probe and that nonspecific DNA-protein interaction modes exhibit some similarity to specific DNA-protein binding modes. These results led us to a novel method that predicts DNA-binding sites and binding-modes for a DNA-binding protein without knowing its specific DNA target sequence. In benchmark tests, the method achieves significantly better performance than three previously established methods, which are based on sophisticated machine-learning techniques. We further apply our method to protein structures predicted through modeling and demonstrate that our method performs satisfactorily on protein models up to 5 A from their native structures.