The SAMPL4 hydration challenge: evaluation of partial charge sets with explicit-water molecular dynamics simulations

Muddana, Hari S.; Sapra, Neil V.; Fenley, Andrew T.; Gilson, Michael K.

doi:10.1007/s10822-014-9714-6

Cited by 40 publications

(80 citation statements)

References 54 publications

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“…This new parameter set outperforms our standard approach as represented by submission 004. Submission 544 applies standard AM1-BCC GAFF alchemical free energy calculations in GROMACS, and is nearly identical to submission 004 (but done independently in a different lab)[23]. It is worth briefly highlighting key metrics for these methods as well (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Blind prediction of solvation free energies from the SAMPL4 challenge

Mobley

Wymer

Lim

et al. 2014

J Comput Aided Mol Des

151

228

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Here, we give an overview of the small molecule hydration portion of the SAMPL4 challenge, which focused on predicting hydration free energies for a series of 47 small molecules. These gas-to-water transfer free energies have in the past proven a valuable test of a variety of computational methods and force fields. Here, in contrast to some previous SAMPL challenges, we find a relatively wide range of methods perform quite well on this test set, with RMS errors in the 1.2 kcal/mol range for several of the best performing methods. Top-performers included a quantum mechanical approach with continuum solvent models and functional group corrections, alchemical molecular dynamics simulations with a classical all-atom force field, and a single-confor-mation Poisson-Boltzmann approach. While 1.2 kcal/mol is still a significant error, experimental hydration free energies covered a range of nearly 20 kcal/mol, so methods typically showed substantial predictive power. Here, a substantial new focus was on evaluation of error estimates, as predicting when a computational prediction is reliable vs. unreliable has considerable practical value. We found, however, that in many cases errors are substantially underestimated, and that typically little effort has been invested in estimating likely error. We believe this is an important area for further research.

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Section: Resultsmentioning

confidence: 99%

Blind prediction of solvation free energies from the SAMPL4 challenge

Mobley

Wymer

Lim

et al. 2014

J Comput Aided Mol Des

151

228

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“…In computational chemistry, hydration free energies are of particular importance because they are frequently used in force field parameterization 26–29 and in the testing of free energy methods and force fields. 1,8–14,30–37 Furthermore, computed free energies are in some cases found to be accurate enough to highlight problems with experiments and assist in curation of experimental data. 13,38 …”

Section: Introductionmentioning

confidence: 95%

“…In this paper we focus on alchemical free energy calculations, which have been one of the most consistently reliable methods in recent applications such as the SAMPL series of challenges. 1,8–14,25 Consider a pair of end states A and B , and their respective Hamiltonians ℋ A ( q , p ; λ ) and ℋ B ( q , p ; λ ).…”

Section: Theory and Practical Aspects Of Alchemical Calculationsmentioning

confidence: 99%

Approaches for Calculating Solvation Free Energies and Enthalpies Demonstrated with an Update of the FreeSolv Database

et al. 2017

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Solvation free energies can now be calculated precisely from molecular simulations, providing a valuable test of the energy functions underlying these simulations. Here, we briefly review “alchemical” approaches for calculating the solvation free energies of small, neutral organic molecules from molecular simulations, and illustrate by applying them to calculate aqueous solvation free energies (hydration free energies). These approaches use a non-physical pathway to compute free energy differences from a simulation or set of simulations and appear to be a particularly robust and general-purpose approach for this task. We also present an update (version 0.5) to our FreeSolv database of experimental and calculated hydration free energies of neutral compounds and provide input files in formats for several simulation packages. This revision to FreeSolv provides calculated values generated with a single protocol and software version, rather than the heterogeneous protocols used in the prior version of the database. We also further update the database to provide calculated enthalpies and entropies of hydration and some experimental enthalpies and entropies, as well as electrostatic and nonpolar components of solvation free energies.

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“…These sets of charges are then averaged to take account of the electronic polarization of a solute molecule implicitly. Using this scheme, Muddana et al predicted the hydration free energies of the molecules in the SAMPL4 challenge with acceptable accuracy . Mecklenfeld et al also applied this kind of charges to calculate the solvation free energies of 29 drug‐like molecules in 12 diverse solvents and found that the overall performance of the physically motivated IPolQ‐Mod charges and the well‐calibrated restrained electrostatic potential (RESP) charges is similar …”

Section: Introductionmentioning

confidence: 99%

Solvation Free Energy Calculations: The Combination between the Implicitly Polarized Fixed‐charge Model and the Reference Potential Strategy

Jia

2019

J Comput Chem

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The IPolQ‐Mod charges, which are the average of two charge sets fitted in vacuum state and condensed phase, take account of polarization effect implicitly in the solvation free energy calculation. However, the performance of the IPolQ‐Mod charges sensitively depends on the QM levels used to generate the electrostatic potential from which the charges are fitted. In addition, the forces on atoms are not accurate theoretically in the molecular dynamics (MD) simulation as the solvent only feels the electrostatic potential of a half‐polarized density of the solute according to the derivation of the IPolQ‐Mod charges. To study these issues in detail, the IPolQ‐Mod charges are combined with the reference potential (RP) strategy to predict the solvation free energies in the present study. It is found that the thermodynamic perturbation (TP) corrections utilizing total energy difference and interaction energy difference are almost the same and free of bias. The solvation free energies estimated by the RP method match very well with those obtained by applying IPolQ‐Mod charges into MD simulation directly. By means of the RP strategy, the performances of the IPolQ‐Mod charges with the change of the strength of the exact HF exchange in several DFT functionals are determined effectively. Although the “optimal” strengths are found in B3LYP and LC‐ωPBE, the improvements over the default strength are not too much. In addition to the IPolQ‐Mod charges, other charge models like bond charge correction (BCC) charges could also be combined with the RP strategy to study the thermodynamic properties like solvation free energy. © 2019 Wiley Periodicals, Inc.

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The SAMPL4 hydration challenge: evaluation of partial charge sets with explicit-water molecular dynamics simulations

Cited by 40 publications

References 54 publications

Blind prediction of solvation free energies from the SAMPL4 challenge

Blind prediction of solvation free energies from the SAMPL4 challenge

Approaches for Calculating Solvation Free Energies and Enthalpies Demonstrated with an Update of the FreeSolv Database

Solvation Free Energy Calculations: The Combination between the Implicitly Polarized Fixed‐charge Model and the Reference Potential Strategy

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