Assessing the influence of solvation models on structural characteristics of intrinsically disordered protein

Abstract

Intrinsically disordered proteins are associated with functions of signaling and regulation as well as with a number of diseases such as cancer and neurodegenerative conditions. Molecular dynamics simulation is potentially a powerful tool to study those protein conformational disorders in full atomic details that would be difficult to gain from experimental measurements. However, the accuracy of the simulation critically relies on the quality of underlying potential energy functions or force fields. In particular, structural properties of intrinsically disordered proteins are expected to depend more sensitively on protein–water interactions because of their increased solvent exposure than folded globular proteins. Here, we investigate the impact of solvation models on structural characteristics of full-length amyloid-beta (Aβ) protein, an intrinsically disordered protein whose aggregation is linked to Alzheimer’s disease. For this purpose, we performed extensive molecular dynamics simulations by combining AMBER ff99SB force field for protein with differing solvent water models as well as solvation procedures with different solvent box sizes. We find that the structural characteristics of Aβ protein differ remarkably depending on the water model adopted as well as on the solvent box size. Our results demonstrate the significant sensitivity on the solvation procedure including the solvent force field in characterizing structural properties of intrinsically disordered proteins.