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Absolute free energies estimated by combining precalculated molecular fragment libraries
Author(s) -
Zhang Xin,
Mamonov Artem B.,
Zuckerman Daniel M.
Publication year - 2009
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.21337
Subject(s) - fragment (logic) , partition (number theory) , molecule , work (physics) , molecular dynamics , partition function (quantum field theory) , chemistry , function (biology) , computational chemistry , computer science , algorithm , physics , mathematics , thermodynamics , combinatorics , quantum mechanics , organic chemistry , evolutionary biology , biology
The absolute free energy—or partition function, equivalently—of a molecule can be estimated computationally using a suitable reference system. Here, we demonstrate a practical method for staging such calculations by growing a molecule based on a series of fragments. Significant computer time is saved by precalculating fragment configurations and interactions for reuse in a variety of molecules. We use such fragment libraries and interaction tables for amino acids and capping groups to estimate free energies for small peptides. Equilibrium ensembles for the molecules are generated at no additional computational cost and are used to check our results by comparison to standard dynamics simulation. We explain how our work can be extended to estimate relative binding affinities. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009