We have combined and integrated our previously developed library-based Growth and Monte Carlo simulation techniques in order to allow for both thorough sampling and free energy measurements of all-atom peptides. The integrated growth and relaxation technique makes use of pre-calculated Boltzmann distributed statistical libraries of molecular-fragments and their corresponding energies . Due to this new implementation, we are now able to accurately determine free energies and sample phase space for larger systems that were previously unattainable with library-based growth. We report sampling quality and statistics on free energy measurements for four polypeptide systems that we examined. We discuss possible applications of this new and more general library-based method .
Pre-calculated libraries of molecular fragment configurations have previously been used as a basis for both equilibrium sampling (via " library-based Monte Carlo") and for obtaining absolute free energies using a polymer-growth formalism. Here, we combine the two approaches to extend the size of systems for which free energies can be calculated. We study a series of all-atom poly-alanine systems in a simple dielectric "solvent" and find that precise free energies can be obtained rapidly. For instance, for 12 residues, less than an hour of single-processor is required. The combined approach is formally equivalent to the "annealed importance sampling" algorithm; instead of annealing by decreasing temperature, however, interactions among fragments are gradually added as the molecule is "grown." We discuss implications for future binding affinity calculations in which a ligand is grown into a binding site .
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We have combined and integrated our previously developed
Pre-calculated libraries of molecular fragment configurations have previously been used as a basis for both equilibrium sampling (via "
R
Growth and Monte Carlo simulation techniques in order to allow for both thorough sampling and free energy measurements of
Monte Carlo") and for obtaining absolute free energies using a polymer-growth formalism. Here, we combine the two approaches to extend the size of systems for which free energies can be calculated. We study a series of
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peptides. The integrated growth and relaxation technique makes use of pre-calculated Boltzmann distributed statistical libraries of molecular-fragments and their corresponding energies . Due to this new implementation, we are now able to accurately determine free energies and sample phase space for larger systems that were previously unattainable with library-based growth. We report sampling quality and statistics on free energy measurements for four polypeptide systems that we examined. We discuss possible applications of this new and more general library-based method
poly-alanine systems in a simple dielectric "solvent" and find that precise free energies can be obtained rapidly. For instance, for 12 residues, less than an hour of single-processor is required. The combined approach is formally equivalent to the "annealed importance sampling" algorithm; instead of annealing by decreasing temperature, however, interactions among fragments are gradually added as the molecule is "grown." We discuss implications for future binding affinity calculations in which a ligand is grown into a binding site