LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions

Wallace, Andrew; Laskowski, Roman A.; Thornton, Janet M.

doi:10.1093/protein/8.2.127

Cited by 5,108 publications

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“…This is important evidence, since the siRNA approach is an acute insult to the cells, while a knockout cell line can undergo adaptive differential expression of genes, potentially obscuring the direct effect of the knockout genotype. (Hartshorn, 2002), while those in (b) and (d) were prepared using Ligplot (Wallace et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

α-Tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II

et al. 2008

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a-Tocopheryl succinate (a-TOS) is a selective inducer of apoptosis in cancer cells, which involves the accumulation of reactive oxygen species (ROS). The molecular target of a-TOS has not been identified. Here, we show that a-TOS inhibits succinate dehydrogenase (SDH) activity of complex II (CII) by interacting with the proximal and distal ubiquinone (UbQ)-binding site (Q P and Q D , respectively). This is based on biochemical analyses and molecular modelling, revealing similar or stronger interaction energy of a-TOS compared to that of UbQ for the Q P and Q D sites, respectively. CybL-mutant cells with dysfunctional CII failed to accumulate ROS and underwent apoptosis in the presence of a-TOS. Similar resistance was observed when CybL was knocked down with siRNA. Reconstitution of functional CII rendered CybL-mutant cells susceptible to a-TOS. We propose that a-TOS displaces UbQ in CII causing electrons generated by SDH to recombine with molecular oxygen to yield ROS. Our data highlight CII, a known tumour suppressor, as a novel target for cancer therapy.

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Section: Discussionmentioning

confidence: 99%

α-Tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II

et al. 2008

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“…The two top scoring compounds were investigated to study their molecular interactions with the protein molecule. The hydrophobic interactions and H-bonds were calculated using the Ligplot program [20]. H-bonds were taken into consideration when the distance between acceptor-donor atoms was less than 3.3 Å, with maximum hydrogen-acceptor atom distance of 2.7Å and acceptor-H-donor angle greater than 90°.…”

Section: Methodsmentioning

confidence: 99%

Structural insights into mode of actions of novel natural Mycobacterium protein tyrosine phosphatase B inhibitors

et al. 2014

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BackgroundTuberculosis has become a major health problem being the second leading cause of death worldwide. Mycobacterium tuberculosis secretes a virulence factor, protein tyrosine phosphatase B (mPTPB) in the cytoplasm of host macrophage which suppresses its natural innate immune response and helps the pathogen survive and proliferate in the phagosome. The present study aims at indentifying potent inhibitors of mPTPB by using computational approaches of ligand based molecular modeling and docking studies.ResultsA 3D QSAR model was developed using a set of benzofuran salicylic acid based mPTPB inhibitors with experimentally known IC50 values. The model was generated using the statistical method of principle component regression analysis in combination with step wise forward variable selection algorithm. It was observed that steric and hydrophobic descriptors positively contribute towards the inhibitory activity of the ligands. The developed model had a robust internal as well as external predictive power as indicated by the q2 value of 0.8920 and predicted r2 value of 0.8006 respectively. Hence, the generated model was used to screen a large set of naturally occurring chemical compounds and predict their biological activity to identify more potent natural compounds targeting mPTPB. The two top potential hits (with pIC50 value of 1.459 and 1.677 respectively) had a similar interaction pattern as that of the most potent compound (pIC50 = 1.42) of the congeneric series.ConclusionThe contour plot provided a better understanding of the relationship between structural features of substituted benzofuran salicylic acid derivatives and their activities which would facilitate design of novel mPTPB inhibitors. The QSAR modeling was used to obtain an equation, correlating the important steric and hydrophobic descriptors with the pIC50 value. Thus, we report two natural compounds of inhibitory nature active against mPTPB enzyme of Mycobacterium tuberculosis. These inhibitors have the potential to evolve as lead molecules in the development of drugs for the treatment of tuberculosis.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-S1-S3) contains supplementary material, which is available to authorized users.

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“…The compound set was divided into two sets, namely, the training and test set with each containing 60 and 24 proline-based inhibitors, respectively. The structures in the test set were selected randomly, and they were as 24 to identify some specific contacts between atoms of ligand and receptor. Some of these ligand atoms were served as the correspondence points in the subsequent structural alignment processes.…”

Section: Methodsmentioning

confidence: 99%

A Ligand-Based Molecular Modeling Study on Some Matrix Metalloproteinase-1 Inhibitors Using Several 3D QSAR Techniques

Tsai

Lin

2004

J. Chem. Inf. Comput. Sci.

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Some three-dimensional quantitative structure-activity relationship (3D-QSAR) models have been constructed using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices (CoMSIA) for a series of 84 proline-based plus 12 structurally more diversified nonproline matrix metalloproteinase inhibitors. The structures of these inhibitors were built from a structure template extracted from the crystal structure of stromelysin. The structures built were divided into the training and test sets for both the CoMFA and CoMSIA analyses for each being composed of 60 and 24 inhibitors, respectively. The structures in the training set were aligned using some alignment rules derived from the analysis of the Ligplot program on a recent crystal structure of ligand-collagenase-1 complex. Some stepwise CoMSIA's were performed on the aligned training set on which the best CoMFA result was obtained. The best CoMSIA model was identified from the stepwise results, and the corresponding pharmacophore features were used for the construction of a pharmacophore hypothesis by the Catalyst 4.9 program. The training set was extended to include 11 structurally more diversified and nonproline inhibitors. To construct a pharmacophore hypothesis, the conformation of 60 structurally aligned proline-based inhibitors was fixed, while that of the 11 structurally more diversified nonproline inhibitors was allowed to vary during the hypothesis construction process. It was found that the predicted activities by the top hypothesis constructed for both the training and test sets were as good in statistics as those predicted by the best CoMSIA model from which the hypothesis was derived. The top hypothesis was mapped onto the structures of several highly active inhibitors selected from both the training and test sets. The goodness of mapping on each inhibitor was found to be correlated well with the activity of each inhibitor.

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LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions

Cited by 5,108 publications

References 0 publications

α-Tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II

α-Tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II

Structural insights into mode of actions of novel natural Mycobacterium protein tyrosine phosphatase B inhibitors

A Ligand-Based Molecular Modeling Study on Some Matrix Metalloproteinase-1 Inhibitors Using Several 3D QSAR Techniques

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