PROTEIN MODELS: A COMPUTATIONAL APPROACH TO FOLDING AND AGGREGATION PHENOMENA

Square lattice protein models are used to study the competition between folding and aggregation phenomena. The problem is approached by considering Metropolis Monte Carlo simulations of non-isolated lattice protein models; different protein molecules can interact each other and, in competition with folding, can aggregate by forming dimers. The calculations take in exam the behavior of three types of proteins: a) proteins with a very well designed sequence (good folders); b) proteins which folding kinetics present kinetic partitioning effects (intermediate folders); c) small proteins with native states having the geometry of pure secondary structure motives (like alpha helices or beta sheets). The results show that good folders very rarely form aggregates; on the contrary, in almost all considered cases, intermediate folders display high tendency to form dimers. Finally, alpha helices display a low tendency to aggregate in comparison to that found for beta-sheets. However, also for these systems, structural intermediates in the folding kinetics can strongly influence the aggregation tendency.