On the use of knowledge-based potentials for the evaluation of models of protein-protein, protein-DNA, and protein-RNA interactions

Abstract

Proteins are the bricks and mortar of cells, playing structural and functional roles. In order to perform their function, they interact with each other as well as with other biomolecules such as DNA or RNA. Therefore, to fathom the function of a protein, we require knowing its partners and the atomic details of its interactions (i.e., the structure of the complex). However, the amount of protein interactions with an experimentally determined three-dimensional structure is scarce. Therefore, computational techniques such as homology modeling are foremost to fill this gap. Protein interactions can be modeled using as templates the interactions of homologous proteins, if the structure of the complex is known, or using docking methods. In both approaches, the estimation of the quality of models is essential. There are several ways to address this problem. In this review, we focus on the use of knowledge-based potentials for the analysis of protein interactions. We describe the procedure to derive statistical potentials and split them into different energetic terms that can be used for different purposes. We extensively discuss the fields where knowledge-based potentials have been successfully applied to (1) model protein-protein, protein-DNA, and protein-RNA interactions and (2) predict binding sites (in the protein and in the DNA). Moreover, we provide ready-to-use resources for docking and benchmarking protein interactions.

Keywords: Binding-site prediction; Docking; Knowledge-based potentials; Protein interaction modeling; Protein–DNA interactions; Protein–protein interactions.