Short Polypeptide with Metastable Structures

Abstract

Proteins spontaneously fold into a specific native structure, and thereby function in living cell. If a large protein has metastable structures, it is expected that misfolding occurs. In contrast, for a short part cut out from a large protein, the misfolding is often presumed to be absent. For example, the so-called intrinsically disordered (ID) region is experimentally known to take a fluctuating state. On the other hand, many low energy structures of a short ID region is obtained by the molecular dynamics simulation and therefore the short ID region is expected to exhibit misfolding. The shortness of the ID region may resolve this inconsistency. To shed light on the effect of the shortness, we investigate a short polypeptide into which the simulated structures are embedded as rigid structures by employing the associative memory model. We show that the misfolding occurs even in the short polypeptide because the free energy barriers between the embedded metastable states are sufficiently high. This result indicates that the shortness of the polypeptide is not sufficient to explain the fluctuation observed in the experiment. Therefore we expect that all the simulated structures are not so rigid and the short ID region actually fluctuates largely from these structures.