Extending fragment-based free energy calculations with library Monte Carlo simulation: annealing in interaction space |
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Authors: | Lettieri Steven Mamonov Artem B Zuckerman Daniel M |
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Affiliation: | Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. |
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Abstract: | 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 time 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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Keywords: | free energy library‐based Monte Carlo library‐based growth peptides annealed importance sampling |
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