Topology-based potentials and the study of the competition between protein folding and aggregation

Abstract

Topology-based or Go-type potentials have been shown to be very useful in the understanding of the relations between the structure of the native state of a protein and some of its folding characteristics. A different question is whether they can also make such a contribution when the aggregation process of misfolded or partially folded structures is under study. In this work, in spite of the obvious trend of these simulation models toward the native state, we show that there are some aspects about aggregation that can be addressed by topology-based potentials: the role of the thermodynamic characteristics of the transition on preventing the aggregation process, or the larger propensity of highly symmetric protein structures to form domain swapped dimers. In a second part of this work, we use the possibilities of computer simulation as a design of numerical experiments to analyze the fundamental role of intermediate states in the aggregation process of globular proteins.