Developing an explicit solvent model for protein aggregation

Protein aggregation is responsible for amyloid formation and implicated in many neurological diseases. Since protein aggregation is a slow process, intermediate resolution protein models with implicit solvent have been developed to extend the time scale accessible to computer simulations. These models have been improved over many years and have become a valuable tool to support and interpret experimental work on protein aggregation. However, explicit solvent models are required to describe such processes as thermophoresis, which has recently become a tool to study fibril formation. In this work, we start from an off-lattice, mesoscale protein model with implicit solvent to develop an explicit solvent model that reproduces the equilibrium conformational and aggregation properties of the original model. To this end, we choose a solvent that is compatible with the protein model and perform simulations where the interaction parameters are adjusted during the simulation to match the desired properties. Applying the approach to short peptides in water, we find that solvent-solvent interactions are essential.