UC Irvine

Realistic biological conditions are characterized by high concentrations of biomolecular solutes. Protein conformations and protein-protein interactions can be affected by crowding. The inclusion of a high number of proteins to model such environments necessitates the use of computationally inexpensive methods, such as rigid-body Brownian dynamics or Monte Carlo (MC) simulations. However, the rigid body representation of many protein systems gives rise to artifacts in protein-protein interactions. Presented here is the multi-conformational Monte Carlo (mcMC) method that avoids such artifacts by incorporating molecular flexibility at a low computational cost. We employ it to study the interaction of eye lens proteins, crystallins. In a healthy eye lens crystallins are the structure proteins. Their solubility at concentrations exceeding 400 mg/mL ensures lens transparency. The aggregation of crystallins leads to lens opacification, called cataract. We study how known point mutations associated with cataract formation lead to altered protein-protein interaction and creation of large aggregates.