Open3DQSAR: a new open-source software aimed at high-throughput chemometric analysis of molecular interaction fields.
ABSTRACT Open3DQSAR is a freely available open-source program aimed at chemometric analysis of molecular interaction fields. MIFs can be imported from different sources (GRID, CoMFA/CoMSIA, quantum-mechanical electrostatic potential or electron density grids) or generated by Open3DQSAR itself. Much focus has been put on automation through the implementation of a scriptable interface, as well as on high computational performance achieved by algorithm parallelization. Flexibility and interoperability with existing molecular modeling software make Open3DQSAR a powerful tool in pharmacophore assessment and ligand-based drug design.
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ABSTRACT: The selection of the most appropriate protein conformation is a crucial aspect in molecular docking experiments. In order to reduce the errors arising from the use of a single protein conformation, several authors suggest the use of several tridimensional structures for the target. However, the selection of the most appropriate protein conformations still remains a challenging goal. The protein 3D-structures selection is mainly performed based on pairwise root-mean-square-deviation (RMSD) values computation, followed by hierarchical clustering. Herein we report an alternative strategy, based on the computation of only two atom affinity map for each protein conformation, followed by multivariate analysis and hierarchical clustering. This methodology was applied on seven different kinases of pharmaceutical interest. The comparison with the classical RMSD-based strategy was based on cross-docking of co-crystallized ligands. In the case of epidermal growth factor receptor kinase, also the docking performance on 220 known ligands were evaluated, followed by 3D-QSAR studies. In all the cases, the herein proposed methodology outperformed the RMSD-based one.Molecular Diversity 05/2014; · 2.54 Impact Factor
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ABSTRACT: 3D-QSAR and docking studies of 124 falcipain inhibitors, 2-pyrimidinecarbonitrile derivatives as antimalarial drugs have been carried out. Most descriptive components method was used for dividing the compounds into training (94 compounds) and test (30 compounds) sets. The CoMFA and CoMSIA give cross-validated r cv2 and non-cross-validated r ncv2 correlation coefficients as 0.616 and 0.446, and 0.918 and 0.801, respectively. The Open3DQSAR was used as free available software to process the molecular interaction fields (MIFs) generated by CoMFA and CoMSIA of SYBYL 7.3. The models generated by Open3DQSAR on CoMFA and CoMSIA MIFs give r cv2 values of 0.810 and 0.586 and r ncv2 of 0.921 and 0.823, respectively. The external validation indicated that Open3DQSAR models using CoMFA and CoMSIA MIFs possess good predictive power with r pred2 values of 0.946 and 0.662, respectively. Molecular docking was employed to explore the binding mode between these compounds and the receptor, as well as help understanding the structure–activity relationship revealed by CoMFA and CoMSIA.Medicinal Chemistry Research 01/2012; 21(10):2788-2806. · 1.61 Impact Factor
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ABSTRACT: With fossil fuel reserves on the decline, there is increasing focus on the design and development of low-cost organic photovoltaic devices, in particular, dye-sensitized solar cells (DSSCs). The power conversion efficiency (PCE) of a DSSC is heavily influenced by the chemical structure of the dye. However, as far as we know, no predictive quantitative structure-property relationship models for DSSCs with PCE as one of the response variables have been reported. Thus, we report for the first time the successful application of comparative molecular field analysis (CoMFA) and vibrational frequency-based eigenvalue (EVA) descriptors to model molecular structure-photovoltaic performance relationships for a set of 40 coumarin derivatives. The results show that the models obtained provide statistically robust predictions of important photovoltaic parameters such as PCE, the open-circuit voltage (VOC ), short-circuit current (JSC ) and the peak absorption wavelength λmax . Some of our findings based on the analysis of the models are in accordance with those reported in the literature. These structure-property relationships can be applied to the rational structural design and evaluation of new photovoltaic materials. © 2013 Wiley Periodicals, Inc.Journal of Computational Chemistry 01/2014; 35(3):214-226. · 3.60 Impact Factor