Dataset Information

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 ? angles, and the coupling between ring puckering and backbone degrees of freedom.

SUBMITTER: Radhakrishnan A

PROVIDER: S-EPMC3376247 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Improved atomistic Monte Carlo simulations demonstrate that poly-L-proline adopts heterogeneous ensembles of conformations of semi-rigid segments interrupted by kinks.

Radhakrishnan Aditya A Vitalis Andreas A Mao Albert H AH Steffen Adam T AT Pappu Rohit V RV

The journal of physical chemistry. B 20120227 23

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 forcef ...[more]

PMID: 22329658

Similar Datasets

Project description:Förster Resonance Energy Transfer (FRET) experiments probe molecular distances via distance dependent energy transfer from an excited donor dye to an acceptor dye. Single molecule experiments not only probe average distances, but also distance distributions or even fluctuations, and thus provide a powerful tool to study biomolecular structure and dynamics. However, the measured energy transfer efficiency depends not only on the distance between the dyes, but also on their mutual orientation, which is typically inaccessible to experiments. Thus, assumptions on the orientation distributions and averages are usually made, limiting the accuracy of the distance distributions extracted from FRET experiments. Here, we demonstrate that by combining single molecule FRET experiments with the mutual dye orientation statistics obtained from Molecular Dynamics (MD) simulations, improved estimates of distances and distributions are obtained. From the simulated time-dependent mutual orientations, FRET efficiencies are calculated and the full statistics of individual photon absorption, energy transfer, and photon emission events is obtained from subsequent Monte Carlo (MC) simulations of the FRET kinetics. All recorded emission events are collected to bursts from which efficiency distributions are calculated in close resemblance to the actual FRET experiment, taking shot noise fully into account. Using polyproline chains with attached Alexa 488 and Alexa 594 dyes as a test system, we demonstrate the feasibility of this approach by direct comparison to experimental data. We identified cis-isomers and different static local environments as sources of the experimentally observed heterogeneity. Reconstructions of distance distributions from experimental data at different levels of theory demonstrate how the respective underlying assumptions and approximations affect the obtained accuracy. Our results show that dye fluctuations obtained from MD simulations, combined with MC single photon kinetics, provide a versatile tool to improve the accuracy of distance distributions that can be extracted from measured single molecule FRET efficiencies.

Dataset Information

Improved atomistic Monte Carlo simulations demonstrate that poly-L-proline adopts heterogeneous ensembles of conformations of semi-rigid segments interrupted by kinks.

Publications

Improved atomistic Monte Carlo simulations demonstrate that poly-L-proline adopts heterogeneous ensembles of conformations of semi-rigid segments interrupted by kinks.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets