Journal of Computational Chemistry
Journal of Computational Chemistry
5 years ago

Efficient estimation of binding free energies between peptides and an MHC class II molecule using coarse-grained molecular dynamics simulations with a weighted histogram analysis method

Efficient estimation of binding free energies between peptides and an MHC class II molecule using coarse-grained molecular dynamics simulations with a weighted histogram analysis method
Ming Huang, Ronald G. Larson, Fei Wen, Wenjun Huang
We estimate the binding free energy between peptides and an MHC class II molecule using molecular dynamics (MD) simulations with the weighted histogram analysis method (WHAM). We show that, owing to its more thorough sampling in the available computational time, the binding free energy obtained by pulling the whole peptide using a coarse-grained (CG) force field (MARTINI) is less prone to significant error induced by inadequate-sampling than using an atomistic force field (AMBER). We further demonstrate that using CG MD to pull 3–4 residue peptide segments while leaving the remaining peptide segments in the binding groove and adding up the binding free energies of all peptide segments gives robust binding free energy estimations, which are in good agreement with the experimentally measured binding affinities for the peptide sequences studied. Our approach thus provides a promising and computationally efficient way to rapidly and reliably estimate the binding free energy between an arbitrary peptide and an MHC class II molecule. © 2017 Wiley Periodicals, Inc. Knowing the binding free energy between bound peptide and Major Histocompatibility Complex Class II (MHCII) is important to design effective vaccines and therapeutics. In this article, we use Molecular Dynamics simulation with umbrella sampling method and coarse-grained force field to estimate the binding free energy. We also propose a segmented peptide model, which can robustly estimate the binding free energy between bound peptide and MHCII efficiently.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/jcc.24845

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