Performance of CHARMM36m with modified water model in simulating intrinsically disordered proteins: a case study

Molecular dynamics simulations can be a powerful tool to complement experiments in the study of the structures and dynamics of intrinsically disordered proteins. Though the accuracy of the physics-based all-atom force fields has improved significantly in simulating structured proteins over the past twenty years, most of these force fields face a big challenge to simulate flexible proteins. Recently, CHARMM36m with modified TIP3P model was proposed as a possible solution to simulate intrinsically disordered proteins. Here, we tested the proposed solution using an extensively studied protein, namely NCBD, to explore the performance of CHARMM36m plus modified TIP3P water. Our results suggest that the modified TIP3P water model does enhance the sampling of conformational space compared to the standard TIP3P water model. However, the new CHARMM36m force field still leads to over-compact structures and over-stabilized helices.