title: Improved atomistic Monte Carlo simulations demonstrate that poly-L-proline adopts heterogeneous ensembles of conformations of semi-rigid segments interrupted by kinks.
abstract: Poly-L-proline (PLP) polymers are useful mimics of biologically relevant proline-rich sequences. Biophysical and computational studies of PLP polymers in aqueous solutions are challenging because of the diversity of length scales and the slow time scales for conformational conversions. We describe an atomistic simulation approach that combines an improved ABSINTH implicit solvation model, with conformational sampling based on standard and novel Metropolis Monte Carlo moves. Refinements to forcefield parameters were guided by published experimental data for proline-rich systems. We assessed the validity of our simulation results through quantitative comparisons to experimental data that were not used in refining the forcefield parameters. Our analysis shows that PLP polymers form heterogeneous ensembles of conformations characterized by semirigid, rod-like segments interrupted by kinks, which result from a combination of internal cis peptide bonds, flexible backbone ψ angles, and the coupling between ring puckering and backbone degrees of freedom.
authors.affiliation: Department of Biomedical Engineering, Washington University in St. Louis, One Brookings Drive, Campus Box 1097, St. Louis, Missouri 63130, USA.
authors.forename: Aditya
authors.initials: A
authors.lastname: Radhakrishnan
authors.forename: Andreas
authors.initials: A
authors.lastname: Vitalis
authors.forename: Albert H
authors.initials: AH
authors.lastname: Mao
authors.forename: Adam T
authors.initials: AT
authors.lastname: Steffen
authors.forename: Rohit V
authors.initials: RV
authors.lastname: Pappu
mesh_terms: D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D010455:Peptides; C011083:polyproline