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Extending fragment‐based free energy calculations with library monte carlo simulation: Annealing in interaction space
Author(s) -
Lettieri Steven,
Mamonov Artem B.,
Zuckerman Daniel M.
Publication year - 2010
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.21695
Subject(s) - monte carlo method , simulated annealing , statistical physics , formalism (music) , molecule , chemistry , fragment (logic) , dielectric , computational chemistry , physics , computer science , algorithm , mathematics , quantum mechanics , art , musical , statistics , visual arts
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. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011