Rapid sampling of all-atom peptides using a library-based polymer-growth approach.
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.
Mamonov
Artem B
AB
Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Zhang
Xin
X
Zuckerman
Daniel M
DM
D000465:Algorithms; D003198:Computer Simulation; D016208:Databases, Factual; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry
D010455:Peptides; D011108:Polymers