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Comparison of three enveloping distribution sampling Hamiltonians for the estimation of multiple free energy differences from a single simulation
Author(s) -
Christ Clara D.,
Van Gunsteren Wilfred F.
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.21325
Subject(s) - configuration space , thermodynamic integration , sampling (signal processing) , energy (signal processing) , state (computer science) , space (punctuation) , distribution (mathematics) , state space , mathematics , umbrella sampling , statistical physics , physics , molecular dynamics , computer science , algorithm , quantum mechanics , mathematical analysis , statistics , detector , optics , operating system
We test the performance of three different reference state Hamiltonians for enveloping distribution sampling (EDS). EDS is an implementation of umbrella sampling which allows estimation of various free energy differences “on the fly” from a single simulation. This is achieved by construction of a reference state, which envelopes the regions of configuration space important to the various end states of interest. The proposed Hamiltonians differ in the way energy barriers separating these regions of configuration space are reduced. The test system consisted of 17 disubstituted benzenes in water and in complex with α‐cyclodextrin. The calculated free energy differences correlate with thermodynamic integration results ( R 2 > 0.99 for the ligands in water and R 2 > 0.98 for the ligands in complex with α‐cyclodextrin). One of the reference state Hamiltonians outperformed the others in sampling the configuration space important to the various end states. In this reference state not all barriers between all pairs of states are reduced. Instead a minimum spanning tree of states is calculated, which connects states that are “closest” in configuration space. © 2009 Wiley Periodicals, Inc. J Comput Chem 2009