Protein Folding Simulations: Combining Coarse-grained Models and All-atom Molecular Dynamics

The investigation of protein folding and its ramifications in biological contexts is at the heart of molecular biology. Theoretical and computational studies provide a steadily growing contribution to the understanding of factors driving a given polypeptide sequence into the native state. Simplified coarse-grained protein models have proven very useful to gain insights into the general thermodynamic and kinetic features of the folding process. On the other hand, all-atom simulations allow to follow, with microscopic detail, the delicate interplay of the various chemical interactions leading to the formation of the native or intermediate states. In this paper we will discuss different computational strategies employed to tackle the protein folding problem, based on the use of either coarse-grained or all-atom protein descriptions. Finally we will discuss a recent approach that allows to extend the reach of ordinary folding simulations by using a simplified description of protein structures and energy functional in conjunction with all-atom molecular dynamics.