Predicting protein-DNA binding modes

Abstract

Transcriptor factor proteins bind DNA to regulate gene expression. Structural prediction of how they bind has been challenged by two factors: (1) DNA exhibits a large degree of deformation when binding some proteins and (2) the large electrostatic component of the interaction. This leads to well known sampling and scoring failures in docking methodologies, which has limited the use of this technique for studying protein-DNA interactions. We present an approach, MELD-DNA, which combines knowledge from the binding domain of the protein with simulations to predict bound conformations.