Performance of the IEF-MST solvation continuum model in the SAMPL2 blind test prediction of hydration and tautomerization free energies

Soteras, Ignacio; Orozco, Modesto; Luque, F. Javier

doi:10.1007/s10822-010-9331-y

Cited by 24 publications

(28 citation statements)

References 45 publications

(45 reference statements)

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“…We expect that the proper application of any of the following seven methods (All-atom MD [77], multiconformer implicit solvation models such as COSMO-RS [78] and EPIC [79], and the FiSH [80], IEF-PCM [81], SM8 [8], or ZAP [82,83] implicit solvation methods which used single conformers) should lead to, with 95% confidence, transfer energies predictions within 2.0 kcal/mol of the experimental value for new unknowns. However, the average error for each of these methods has a greater than 95% chance of being larger than 1 kcal/mol, indicating there is still room for improvement.…”

Section: Resultsmentioning

confidence: 99%

“…Because the tautomer challenge involved only a few similar transitions, it is difficult to draw general conclusion about tautomer prediction from this exercise alone. For the aqueous transfer portions of the thermodynamic cycle, several solvation models may prove reliable (vide supra), but the methods of Luque [81], Klamt [78], and Kast [84] have all been demonstrated to perform equivalently well.…”

Section: Resultsmentioning

confidence: 99%

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The SAMPL2 blind prediction challenge: introduction and overview

Geballe¹,

Skillman²,

Nicholls³

et al. 2010

J Comput Aided Mol Des

206

240

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The interactions between a molecule and the aqueous environment underpin any process that occurs in solution, from simple chemical reactions to protein-ligand binding to protein aggregation. Fundamental measures of the interaction between molecule and aqueous phase, such as the transfer energy between gas phase and water or the energetic difference between two tautomers of a molecule in solution, remain nontrivial to predict accurately using current computational methods. SAMPL2 represents the third annual blind prediction of transfer energies, and the first time tautomer ratios were included in the challenge. Over 60 sets of predictions were submitted, and each participant also attempted to estimate the error in their predictions, a task that proved difficult for most. The results of this blind assessment of the state of the field for transfer energy and tautomer ratio prediction both indicate where the field is performing well and point out flaws in current methods.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The SAMPL2 blind prediction challenge: introduction and overview

Geballe¹,

Skillman²,

Nicholls³

et al. 2010

J Comput Aided Mol Des

206

240

View full text Add to dashboard Cite

show abstract

“…Hence, the discrepancies were attributed to the inaccuracies of the SMx models [84]. In contrast, the analogous discrepancies observed for the IEF-MST solvation model were interpreted as caused by particularly important higher correlation effects in pyrazolones and isoxazolones [120]. No such distinction between tautomeric systems 1-8 and 10-16 is apparent for the COSMO-RS and EC-RISM calculations (Figure 13.4).…”

Section: The Sampl2 Challenge Of Predicting Tautomer Ratiosmentioning

confidence: 91%

“…Experimental K T values of the SAMPL2 challenge refer to aqueous solution and hence test not only for the reliability of the computational procedure used to obtain gas-phase energy differences but also and specifically the performance of the solvation model. These included mainly continuum models, IEF-MST [120] SMx (x = 8, 8AD, D) [84], and COSMO-RS [130]. As an example of an explicit solvent model, a variant of the three-dimensional reference interaction site model (embedded cluster 3D-RISM) was used [125].…”

Section: The Sampl2 Challenge Of Predicting Tautomer Ratiosmentioning

confidence: 99%

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Quantum Chemical Calculation of Tautomeric Equilibria

Fabian

2013

Tautomerism

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IntroductionTautomerism can be considered as a special case of isomerism where the movement of an atom or group of atoms between two sites occurs rapidly enough to establish chemical equilibrium at room temperature. Hence, both thermodynamic as well as kinetic criteria have to be used to draw an approximate distinction line between tautomerism and conventional isomerism. Assuming a lower limit of K = 10 −8 for the experimental determination of equilibrium constants and a rate constant of k = 10 −5 s −1 distinguishing mobile systems from stable ones, at room temperature G • < 8 kcal mol −1 and G = < 25 kcal mol −1 characterize a tautomeric system [1]. Most interconversion between the individual species occurs by movement of a hydrogen atom (prototropism), as in simple keto-enol [2], lactam-lactim, and annular prototropism in heterocycles [3], or azo-hydrazo [4] tautomerism. Transformation between tautomeric structures by movement of atoms other than hydrogen involves formation of cyclic acetals/ketals, for example, furanose/pyranose forms of sugars, ring-chain tautomerism in oxo carboxylic acid derivatives [1], or azido-tetrazole and related equilibria [5]. Coping with tautomeric equilibria has become a hot topic in chemoinformatics as well as drug discovery. Obviously, reliable predictions of tautomeric equilibria by computational procedures would be of great help. This importance is also revealed by the fact that in the third round of the statistical assessment of the modeling of proteins and ligands (SAMPL) challenge (SAMPL2) the calculation of tautomer energies was included [6]. However, as stated by Martin [7], ''In summary, although quantum chemical calculations provide much insight into the relative energies of tautomers, there appears to be no consensus on the optimal method.'' Frequently, energy differences are quite small and hence require very accurate calculations which can be fiendishly difficult. Thus, the choice of an appropriate electronic structure procedure is very important. Furthermore, environmental influences (solvent) have a profound effect on the position of tautomeric equilibria. Consequently, a proper description of solvation is essential. Alternatively, some property that might be useful to distinguish between tautomers could be Tautomerism: Methods and Theories, First Edition. Edited by Liudmil Antonov.

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Computational Study of Proton Transfer in Tautomers of 3‐ and 5‐Hydroxypyrazole Assisted by Water

et al. 2015

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The tautomerism of 3- and 5-hydroxypyrazole is studied at the B3LYP, CCSD and G3B3 computational levels, including the gas phase, PCM-water effects, and proton transfer assisted by water molecules. To understand the propensity of tautomerization, hydrogen-bond acidity and basicity of neutral species is approached by means of correlations between donor/acceptor ability and H-bond interaction energies. Tautomerism processes are highly dependent on the solvent environment, and a significant reduction of the transition barriers upon solvation is seen. In addition, the inclusion of a single water molecule to assist proton transfer decreases the barriers between tautomers. Although the second water molecule further reduces those barriers, its effect is less appreciable than the first one. Neutral species present more stable minima than anionic and cationic species, but relatively similar transition barriers to anionic tautomers.

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Performance of the IEF-MST solvation continuum model in the SAMPL2 blind test prediction of hydration and tautomerization free energies

Cited by 24 publications

References 45 publications

The SAMPL2 blind prediction challenge: introduction and overview

The SAMPL2 blind prediction challenge: introduction and overview

Quantum Chemical Calculation of Tautomeric Equilibria

Computational Study of Proton Transfer in Tautomers of 3‐ and 5‐Hydroxypyrazole Assisted by Water

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