Multiple protein-DNA interfaces unravelled by evolutionary information, physico-chemical and geometrical properties

Abstract

The usage made of protein surfaces by nucleic acids still remains largely unknown, due to the lack of available structural data and the inherent complexity associated to protein surface deformability and evolution. In this work, we present a method that contributes to decipher such complexity by predicting protein-DNA interfaces and characterizing their properties. It relies on three biologically and physically meaningful descriptors, namely evolutionary conservation, physico-chemical properties and surface geometry. We carefully assessed its performance on several hundreds of protein structures. We achieve a higher sensitivity compared to state-of-the-art methods, and similar precision. Importantly, we show that our method is able to unravel hidden binding sites by applying it to unbound protein structures and to proteins binding to DNA via multiple sites and in different conformations. It is implemented as a fully automated tool, [Formula], freely accessible at: http://www.lcqb.upmc.fr/JET2DNA. We also provide a new reference dataset of 187 protein-DNA complex structures, representative of all types of protein-DNA interactions, along with a subset of associated unbound structures: http://www.lcqb.upmc.fr/PDNAbenchmarks.