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Markov modeling of peptide folding in the presence of protein crowders

Daniel Nilsson1, Sandipan Mohanty2, Anders Irbäck1

  • 1Computational Biology and Biological Physics, Department of Astronomy and Theoretical Physics, Lund University, Sölvegatan 14A, SE-223 62 Lund, Sweden.

The Journal of Chemical Physics
|February 10, 2018
PubMed

Insights

Markov state models reveal protein crowders stabilize peptides. Interacting crowders, like BPTI and GB1, reduce peptide unfolding rates, influencing peptide dynamics and folding.

Area of Science:

  • Computational Biophysics
  • Protein Dynamics
  • Statistical Mechanics

Background:

  • Understanding peptide and protein dynamics is crucial in molecular biology.
  • Protein crowders significantly influence biomolecular behavior, but their precise effects are complex.
  • Markov state models (MSMs) offer a powerful framework for analyzing complex molecular dynamics.

Purpose of the Study:

  • To analyze the dynamics of a β-hairpin-forming peptide in the presence of interacting protein crowders.
  • To investigate the influence of different crowder types (BPTI and GB1) on peptide folding and unfolding rates.
  • To estimate dominant relaxation times of the peptide using Markov state models.

Main Methods:

  • Utilized Monte Carlo (MC) simulations to model peptide-crowder interactions.
  • Constructed Markov state models (MSMs) with varying time resolutions (lag times).
  • Employed MSM eigenfunctions and autocorrelation data fitting for relaxation time estimation.

Main Results:

  • Identified four to five major free-energy minima in the simulated systems.
  • Demonstrated stable estimation of peptide relaxation times using MSM eigenfunctions, even at small lag times.
  • Observed a stabilizing effect of protein crowders on the peptide, particularly BPTI crowders.
  • Attributed the stabilization to a reduced unfolding rate (ku) with largely unchanged folding rate (kf).

Conclusions:

  • Markov state models effectively capture peptide dynamics in the presence of crowders.
  • Protein crowders, especially BPTI, significantly stabilize the β-hairpin peptide by slowing down unfolding.
  • MSM eigenfunctions provide robust estimates of relaxation times, crucial for understanding molecular kinetics.

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