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Relative solvation free energies calculated using an ab initio QM/MM-based free energy perturbation method: dependence of results on simulation length

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Abstract

Molecular dynamics (MD) simulations in conjunction with thermodynamic perturbation approach was used to calculate relative solvation free energies of five pairs of small molecules, namely; (1) methanol to ethane, (2) acetone to acetamide, (3) phenol to benzene, (4) 1,1,1 trichloroethane to ethane, and (5) phenylalanine to isoleucine. Two studies were performed to evaluate the dependence of the convergence of these calculations on MD simulation length and starting configuration. In the first study, each transformation started from the same well-equilibrated configuration and the simulation length was varied from 230 to 2,540 ps. The results indicated that for transformations involving small structural changes, a simulation length of 860 ps is sufficient to obtain satisfactory convergence. In contrast, transformations involving relatively large structural changes, such as phenylalanine to isoleucine, require a significantly longer simulation length (>2,540 ps) to obtain satisfactory convergence. In the second study, the transformation was completed starting from three different configurations and using in each case 860 ps of MD simulation. The results from this study suggest that performing one long simulation may be better than averaging results from three different simulations using a shorter simulation length and three different starting configurations.

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Correspondence to M. Rami Reddy.

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10822_2009_9300_MOESM1_ESM.doc

Partial atomic charges and optimized geometries of all the solute molecules are submitted in the supplementary material. (DOC 40 kb)

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Reddy, M.R., Erion, M.D. Relative solvation free energies calculated using an ab initio QM/MM-based free energy perturbation method: dependence of results on simulation length. J Comput Aided Mol Des 23, 837–843 (2009). https://doi.org/10.1007/s10822-009-9300-5

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  • DOI: https://doi.org/10.1007/s10822-009-9300-5

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