Rapid sampling of all-atom peptides using a library-based polymer-growth approach

Physics – Biological Physics

Scientific paper

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Scientific paper

We adapted existing polymer growth strategies for equilibrium sampling of peptides described by modern atomistic forcefields with implicit solvent. The main novel feature of our approach is the use of pre-calculated statistical libraries of molecular fragments. A molecule is sampled by combining fragment configurations -- of single residues in this study -- which are stored in the libraries. Ensembles generated from the independent libraries are reweighted to conform with the Boltzmann factor distribution of the forcefield describing the full molecule. In this way, high-quality equilibrium sampling of small peptides (4-8 residues) typically requires less than one hour of single-processor wallclock time and can be significantly faster than Langevin simulations. Furthermore, approximate but clash-free ensembles can be generated for larger peptides (e.g., 16 residues) in less than a minute of single-processor computing. We also describe an application to free energy calculation, a "multi-resolution" implementation of the growth procedure and application to fragment assembly protein-structure prediction protocols.

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