Solvent–amino acid interaction energies in 3-D-lattice MC simulations of model proteins. Aggregation thermodynamics and kinetics

Recently, we devised an energy scale to vary systematically amino acid–solvent interactions for Monte Carlo simulations of lattice model proteins in water. For 27-mer and 64-mer protein chains, changes in the interaction energies produce quite different protein-folding behavior. Here, for two- to six-chain systems, we investigate the effect of interaction parameters and chain length on protein aggregation. Here too, small changes in the interaction energies produce different classes of protein behavior: non-aggregating; reversibly aggregating; irreversibly aggregating while maintaining part or all of the native structure. Interaction parameters optimized for fast folding and high cooperativity in single-chain simulations provide the least aggregation in multi-chain simulations. Simulations with 27-mers and with 64-mers suggest that the interaction-energy parameters optimal for stability against aggregation depend only weakly on protein size. Although we are not able to find an energy parameter set for 27-mers that makes the native, non-aggregating state the most stable state, we have obtained such a set of parameters for 64-mers, indicating a strong influence of chain length on aggregation properties.