Balanced Protein–Water Interactions Improve Properties of Disordered Proteins and Non-Specific Protein Association

Some frequently encountered deficiencies in all-atom molecular simulations, such as nonspecific protein-protein interactions being too strong, and unfolded or disordered states being too collapsed, suggest that proteins are insufficiently well solvated in simulations using current state-of-the-art force fields. To address these issues, we make the simplest possible change, by modifying the short-range protein-water pair interactions, and leaving all the water-water and protein-protein parameters unchanged. We find that a modest strengthening of protein-water interactions is sufficient to recover the correct dimensions of intrinsically disordered or unfolded proteins, as determined by direct comparison with…

• NI
  National Institute of Diabetes and Digestive and Kidney Diseases
• DO
  Division of Chemical, Bioengineering, Environmental, and Transport Systems

  Award: CBET-1120399