Accelerated cyclic peptide ensemble generation using reservoir REMD

Abstract

Cyclic peptides have been widely used as potential therapeutics and scaffolded antigens due to their ability to bias the conformation to the desired structure using just a few amino acids. Although many tools have been developed to perform cyclic peptide structure prediction, there is little discussion on the ensemble generation of the cyclic peptides. We found that conventional molecular dynamics (MD) simulation is insufficient to sample the ensemble of small cyclic peptides (<10 amino acids), likely due to energy barriers rooted in the ring-like conformational constraint.