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Analyzing the substitution effect on the CoMFA results within the framework of density functional theory (DFT)

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Abstract

Though QSAR was originally developed in the context of physical organic chemistry, it has been applied very extensively to chemicals (drugs) which act on biological systems, in this idea one of the most important QSAR methods is the 3D QSAR model. However, due to the complexity of understanding the results it is necessary to postulate new methodologies to highlight their physical-chemical meaning. In this sense, this work postulates new insights to understand the CoMFA results using molecular quantum similarity and chemical reactivity descriptors within the framework of density functional theory. To obtain these insights a simple theoretical scheme involving quantum similarity (overlap, coulomb operators, their euclidean distances) and chemical reactivity descriptors such as chemical potential (μ), hardness (ɳ), softness (S), electrophilicity (ω), and the Fukui functions, was used to understand the substitution effect. In this sense, this methodology can be applied to analyze the biological activity and the stabilization process in the non-covalent interactions on a particular molecular set taking a reference compound.

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Acknowledgments

Thanks Universidad de Talca (Talca-Chile) through the postdoctoral project N0 3150035 (FONDECYT, CHILE) and thank you very much Dr. Alejandro Toro-labbé associate editor (Journal of Molecular Modeling, JMM).

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Authors and Affiliations

  1. Grupo de Química Cuántica y Teórica de la Universidad de Cartagena, Facultad de Ciencias, Programa de Química, Cartagena de Indias, Colombia

    Alejandro Morales-Bayuelo

  2. FONDECYT Postdoctoral Project N0 3150035, Universidad de Talca, Talca, Chile

    Alejandro Morales-Bayuelo

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  1. Alejandro Morales-Bayuelo
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Correspondence to Alejandro Morales-Bayuelo.

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Morales-Bayuelo, A. Analyzing the substitution effect on the CoMFA results within the framework of density functional theory (DFT). J Mol Model 22, 164 (2016). https://doi.org/10.1007/s00894-016-3036-7

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