title: Toward structure prediction of cyclic peptides.
abstract: Cyclic peptides are a promising class of molecules that can be used to target specific protein-protein interactions. A computational method to accurately predict their structures would substantially advance the development of cyclic peptides as modulators of protein-protein interactions. Here, we develop a computational method that integrates bias-exchange metadynamics simulations, a Boltzmann reweighting scheme, dihedral principal component analysis and a modified density peak-based cluster analysis to provide a converged structural description for cyclic peptides. Using this method, we evaluate the performance of a number of popular protein force fields on a model cyclic peptide. All the tested force fields seem to over-stabilize the α-helix and PPII/β regions in the Ramachandran plot, commonly populated by linear peptides and proteins. Our findings suggest that re-parameterization of a force field that well describes the full Ramachandran plot is necessary to accurately model cyclic peptides.
authors.affiliation: Department of Chemistry, Tufts University, Medford, Massachusetts 02155, USA. yu-shan.lin@tufts.edu.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Yu
authors.forename: Yu-Shan
authors.initials: YS
authors.lastname: Lin
mesh_terms: D056004:Molecular Dynamics Simulation; D010456:Peptides, Cyclic / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D010456:Peptides, Cyclic