caa a22 4500 605510830 CHVBK 20210128100648.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s00894-015-2690-5 doi (NATIONALLICENCE)springer-10.1007/s00894-015-2690-5 Understanding the comparative molecular field analysis (CoMFA) in terms of molecular quantum similarity and DFT-based reactivity descriptors [Elektronische Daten] [Alejandro Morales-Bayuelo, Ricardo Matute, Julio Caballero] The three-dimensional quantitative structure-activity relationship (3D QSAR) models have many applications, although the inherent complexity to understand the results coming from 3D-QSAR arises the necessity of new insights in the interpretation of them. Hence, the quantum similarity field as well as reactivity descriptors based on the density functional theory were used in this work as a consistent approach to better understand the 3D-QSAR studies in drug design. For this purpose, the quantification of steric and electrostatic effects on a series of bicycle [4.1.0] heptane derivatives as melanin-concentrating hormone receptor 1 antagonists were performed on the basis of molecular quantum similarity measures. The maximum similarity superposition and the topo-geometrical superposition algorithms were used as molecular alignment methods to deal with the problem of relative molecular orientation in quantum similarity. In addition, a chemical reactivity analysis using global and local descriptors such as chemical hardness, softness, electrophilicity, and Fukui functions, was developed. Overall, our results suggest that the application of this methodology in drug design can be useful when the receptor is known or even unknown. Springer-Verlag Berlin Heidelberg, 2015 Chemical reactivity descriptors nationallicence Comparative molecular field analysis (CoMFA) nationallicence Density functional theory (DFT) nationallicence Melanin-concentrating hormone receptor 1 (MCH-R1) nationallicence Molecular quantum similarity (MQS) nationallicence 3D-QSAR nationallicence Morales-Bayuelo Alejandro Centro de Bioinformática y Simulación Molecular (CBSM), Universidad de Talca, 2 Norte 685, Casilla 721, Talca, Chile aut Matute Ricardo Departamento de Química, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile aut Caballero Julio Centro de Bioinformática y Simulación Molecular (CBSM), Universidad de Talca, 2 Norte 685, Casilla 721, Talca, Chile aut Journal of Molecular Modeling Springer Berlin Heidelberg 21/6(2015-06-01), 1-10 1610-2940 21:6<1 2015 21 894 https://doi.org/10.1007/s00894-015-2690-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00894-015-2690-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Morales-Bayuelo Alejandro Centro de Bioinformática y Simulación Molecular (CBSM), Universidad de Talca, 2 Norte 685, Casilla 721, Talca, Chile aut NATIONALLICENCE 700 1- Matute Ricardo Departamento de Química, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile aut NATIONALLICENCE 700 1- Caballero Julio Centro de Bioinformática y Simulación Molecular (CBSM), Universidad de Talca, 2 Norte 685, Casilla 721, Talca, Chile aut NATIONALLICENCE 773 0- Journal of Molecular Modeling Springer Berlin Heidelberg 21/6(2015-06-01), 1-10 1610-2940 21:6<1 2015 21 894