74 Novel geometric approaches to uniquely characterize DNA-binding interfaces

Abstract

Protein–nucleic-acid interactions play a critical role in all steps of the gene expression pathway. DNA-binding proteins interact with DNA via distinct regions on their surface that are characterized by an ensemble of chemical, physical, and geometrical properties. In previous studies, we have developed unique approaches to characterize DNA-binding proteins combining geometric and/or electrostatic features (Stawiski et al., 2003; Shazman et al., 2007; Shazman & Mandel-Gutfreund, 2010). Here, I will present a novel approach we have recently developed to characterize protein structures by the distribution of their overlapping local surface patches. In this approach, the protein surface is represented by a bag of overlapping surface patches, which are defined by a central surface residue and its nearest surface neighbors. Using a similar approach to FragBag, a method used to retrieve protein structure neighbors based on short contiguous backbone segments (Budowski-Tal et al., 2010), we characterize each protein by a ‘bag-of-surface patches’ – a vector representing the distribution of different patches which appear on the protein surface. The similarity between two proteins is finally measured by the distance between their corresponding vectors of surface patches. Our results, based on a large benchmark of protein domains, show that the method has a great advantage over other methods for detecting remote function relationships between proteins based solely on the protein surface. We further show the applicability of the method to uniquely identify DNA-binding interfaces accurately and efficiently.