Kinetic of Loop Formation in Polypeptides and Free Energy Landscapes

Abstract

The kinetics of contact formation between the two ends of a polypeptide has been the focus of extended interest in the recent and less recent past. One of the reasons is that contact formation is the elementary event underlying processes such as folding and binding. More importantly, it is experimentally measurable with increasing time and space resolution; it can be predicted theoretically for ideal polymers. Deviations from single exponential kinetics has been sometimes interpreted as a signature of a rugged, protein-like, free energy landscape. Here we present simulations of short peptides with different structural propensity and of a structured protein with different atomistic models. Results show a remarkable deviation from exponentiality for times shorter than a characteristic time that depends on the sequence and length of polypeptides. Deviation from exponentiality cannot be simply explained with the non-Markovian polymer dynamics at very short times, but appears to be characteristic of polypeptides with either specific or non-specific attractive interactions. Our results agree with recent experimental measurements and offer a comprehensive interpretation for them.