Heterogeneous Solvation in Distinctive Protein–Protein Interfaces Revealed by Molecular Dynamics Simulations

Citations Over Time

Abstract

Water, despite being a driving force in biochemical processes, has an elusively complex microscopic behavior. While water can increase its local density near amphiphilic protein surfaces, water is also thought to evaporate from hydrophobic surfaces and cavities, an effect known as "dewetting". The existence and extent of dewetting effects remains elusive due to the difficulty in observing clear "drying" transitions in experiments or simulations. Here, we use explicit solvent molecular dynamics (MD) simulations to study the molecular solvation at the binding interfaces of two distinctive molecular complexes: the highly hydrophilic barnase-barstar and the highly hydrophobic MDM2-p53. Our simulations, in conjunction with simple volumetric analyses, reveal a strikingly different water behavior at the binding interfaces of these two molecular complexes. In both complexes, we observe significant changes in the water local density as the two proteins approach, supporting the existence of a clear dewetting transition in the case of MDM2-p53, with an onset distance of 5.6-7.6 Å. Furthermore, the solvation analysis reported herein is a valuable tool to capture and quantify persistent or transient dewetting events in future explicit solvent MD simulations.

Related Papers

• → Nonpolar Solvation Free Energies of Protein−Ligand Complexes(2010)37 cited
• → Atomic decomposition of the protein solvation free energy and its application to amyloid-beta protein in water(2011)40 cited
• → Assessing the performance of implicit solvation models at a nucleic acid surface(2008)20 cited
• → Comparative Study of Implicit and Explicit Solvation Models for Probing Tryptophan Side Chain Packing in Proteins(2012)4 cited
• → Liquid-state theory derivation of surface accessible solvation potential models for proteins(2002)4 cited