Prediction of the tautomer stability and acidity of phenacylpyridines in aqueous solution

Cedillo, Andrés; Kvedaravičiūtė, Sonata; Aidas, Kęstutis

doi:10.1007/s00214-020-2558-3

Cited by 1 publication

(1 citation statement)

References 57 publications

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“…One type is the empirical scoring method which is based on rules derived from experimental and computational tautomer stability . The other type is the energy-based scoring method which is based on the quantum chemical calculation of internal energy and solvation energy of tautomers. − Oellien et al analyzed sets of tautomer pairs with known preference and developed an empirical scoring method using several rating rules to describe factors related to tautomer stability, including aromaticity, double bond conjugation, specific groups, etc . Milletti et al scored the relative stability of tautomers by using experimental tautomer ratios of 145 representative fragments and p K a of tautomers predicted by MoKa. , Greenwood et al predicted tautomer stability of drug-like molecules by extrapolating from precalculated (DFT/PB-SCRF) tautomer energies of model tautomerizable systems with various substitution effects .…”

Section: Introductionmentioning

confidence: 99%

MolTaut: A Tool for the Rapid Generation of Favorable Tautomer in Aqueous Solution

Pan

Zhao

Zhang

et al. 2023

J. Chem. Inf. Model.

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Fast and proper treatment of the tautomeric states for drug-like molecules is critical in computer-aided drug discovery since the major tautomer of a molecule determines its pharmacophore features and physical properties. We present MolTaut, a tool for the rapid generation of favorable states of drug-like molecules in water. MolTaut works by enumerating possible tautomeric states with tautomeric transformation rules, ranking tautomers with their relative internal energies and solvation energies calculated by AI-based models, and generating preferred ionization states according to predicted microscopic pK a . Our test shows that the ranking ability of the AI-based tautomer scoring approach is comparable to the DFT method (wB97X/6-31G*// M062X/6-31G*/SMD) from which the AI models try to learn. We find that the substitution effect on tautomeric equilibrium is well predicted by MolTaut, which is helpful in computer-aided ligand design. The source code of MolTaut is freely available to researchers and can be accessed at https://github.com/xundrug/moltaut. To facilitate the usage of MolTaut by medicinal chemists, we made a free web server, which is available at http://moltaut.xundrug.cn. MolTaut is a handy tool for investigating the tautomerization issue in drug discovery.

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