Conformational entropy of intrinsically disordered proteins

Protein-protein complexes are essential for the functioning of biomolecules in the cellular environment. The formation of these complexes is typically determined by favorable interactions between proteins resulting in an enthalpic gain exceeding the entropic penalty implied by the ordering process. This loss of entropy is particularly acute in the event that one of the proteins forming the complex is an intrinsically disordered protein, that is, an IDP. Recently, experimental and theoretical works have been published addressing the weight of these free energy contributions in binding processes. In this project we will use computational tools to study the contribution of entropy to protein-protein binding for a series of complexes formed by IDPs. In particular we will use molecular dynamics simulations using state-of-the-art atomistic models and force fields. Using methods originally based on information theory, we will extract entropic contributions to protein binding.