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Tag: Modeling and Simulation

A Discovery of Novel Mycobacterium Tuberculosis Pantothenate Synthetase Inhibitors Based on the Molecular Mechanism of Actinomycin D Inhibition

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Mycobacterium tuberculosis pantothenate synthetase is a potential anti-tuberculosis target, and a high-throughput screening system was previously developed to identify its inhibitors. Using a similar system, we screened a small library of compounds and identified actinomycin D (ActD) as a weak inhibitor of pantothenate synthetase. A new method was established to discover more effective inhibitors by … Continued

Capturing Structure-activity Relationships from Chemogenomic Spaces

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Modeling off-target effects is one major goal of chemical biology, particularly in its applications to drug discovery. Here, we describe a new approach that allows the extraction of structure-activity relationships from large chemogenomic spaces starting from a single chemical structure. Several public source databases, offering a vast amount of data on structure and activity for … Continued

Rethinking 3D-QSAR

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The average error of pIC50 prediction reported for 140 structures in make-and-test applications of topomer CoMFA by four discovery organizations is 0.5. This remarkable accuracy can be understood to result from a topomer pose’s goal of generating field differences only at lattice intersections adjacent to intended structural change.

3D-QSAR Studies on Caspase-mediated Apoptosis Activity of Phenolic Analogs

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Phenols and its analogues are known to induce caspase-mediated apoptosis activity and cytotoxicity on various cancer cell lines. In the current work, two types of molecular field analysis techniques were used to perform the three dimension quantitative structure activity relationship (3D-QSAR) modeling between structural characters and anticancer activity of two sets of phenolic compounds, which … Continued

3D-QSAR Studies and Molecular Docking on [5-(4-amino-1H-benzoimidazol-2-yl)-furan-2-yl]-phosphonic Acid Derivatives as Fructose-1,6-biphophatase Inhibitors

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Fructose-1,6-biphophatase has been regarded as a novel therapeutic target for the treatment of type 2 diabetes mellitus (T2DM). 3D-QSAR and docking studies were performed on a series of [5-(4-amino-1H-benzoimidazol-2-yl)-furan-2-yl]-phosphonic acid derivatives as fructose-1,6-biphophatase inhibitors. The CoMFA and CoMSIA models using thirty-seven molecules in the training set gave rcv2 values of 0.614 and 0.598, r2 values … Continued

Structure-based Quantitative Structure-activity Relationship Studies of Checkpoint Kinase 1 Inhibitors

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Structure-based quantitative structure-activity relationship (QSAR) studies on a series of checkpoint kinase 1 (Chk1) inhibitors were performed to find the key structural features responsible for their inhibitory activity. Molecular docking was employed to explore the binding mode of all inhibitors at the active site of Chk1 and determine the active conformation for the QSAR studies. … Continued

3D-QSAR and Molecular Docking Studies on Derivatives of MK-0457, GSK1070916 and SNS-314 as Inhibitors Against Aurora B Kinase

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Development of anticancer drugs targeting Aurora B, an important member of the serine/threonine kinases family, has been extensively focused on in recent years. In this work, by applying an integrated computational method, including comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), homology modeling and molecular docking, we investigated the structural determinants of … Continued

3D-QSAR Studies of Latrunculin-based Actin Polymerization Inhibitors Using CoMFA and CoMSIA Approaches

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The marine-derived macrolide latrunculins A and B, from the Red Sea sponge Negombata magnifica, are known to reversibly bind actin monomers, forming 1:1 complex with G-actin, disrupting its polymerization. Latrunculins have remarkable physiological properties and widely used as biochemical markers. Nevertheless, no QSAR studies have been developed for any kind of actin disruptors. In the … Continued

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