Abstract
We adapted existing polymer growth strategies for equilibrium sampling of peptides described by modern atomistic forcefields with a simple uniform dielectric solvent. The main novel feature of our approach is the use of precalculated 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, clash-free ensembles can be generated for larger peptides (up to 32 residues in this study) in less than a minute of single-processor computing. We discuss possible applications of our growth procedure to free energy calculation, fragment assembly protein-structure prediction protocols, and to "multi-resolution" sampling.
Original language | English (US) |
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Pages (from-to) | 396-405 |
Number of pages | 10 |
Journal | Journal of Computational Chemistry |
Volume | 32 |
Issue number | 3 |
DOIs | |
State | Published - Feb 2011 |
Externally published | Yes |
Keywords
- equilibrium sampling
- fragment-based
- library-based
- peptides
- polymer-growth
ASJC Scopus subject areas
- General Chemistry
- Computational Mathematics