LigScore: a novel scoring function for predicting binding affinities

Krammer, André; Kirchhoff, Paul D.; Jiang, Xiaohui; Venkatachalam, C. M.; Waldman, Marvin

doi:10.1016/j.jmgm.2004.11.007

Cited by 350 publications

(261 citation statements)

References 43 publications

(56 reference statements)

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“…Docked pose of the compound with protein (Tumour necrosis factor α ) is presented in Figure 1. The dockscore values includes Ligscore 1&2 (Mayo et al, 1990); Piecewise Linear Potential (PLP)-PLP1 (Krammer et al ,2005;Gehlhaar et al, 1995) and PLP 2 (Gehlhaar et al,1995); Jain (Jain 1996) ; Potential of Mean Force-PMF (Mugge and Martin YC, 1999); PMF04 (Mugge, 2006), Ligand internal energy and dockscore obtained using LigandFit protocol of Discovery studio 2.1.…”

Section: Resultsmentioning

confidence: 99%

In Silico analysis of compounds characterized fromPseudarthria viscida root with TNF

Rajan¹

2012

J. App. Pharm. Sci.

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Tumour necrosis factor is a polypeptide cytokine involved in inflammation and the acute phase response. TNF-alpha is present in larger quantities in persons with rheumatoid arthritis. Direct inhibition of TNF-α by the commercial biological agents has produced significant advances in rheumatoid arthritis treatment and validated the extra-cellular inhibition of this proinflammatory cytokine as an effective therapy. However, viable leads molecule that inhibits TNF-α have not been reported . Bioinformatics is seen as an emerging field with the potential to significantly improve how drugs are found brought to the clinical trials and eventually released to the marketplace. Computer-Aided Drug Design (CADD) is a specialized discipline that uses computational methods to stimulate drug-protein interaction. Discovery studio 2.1 provides a set of protocols for predicting and analyzing the interaction between protein and ligands. Molecular Docking experiments were carried out for the compounds identified from Pseudarthria viscida root extract with TNF-alpha using Accelry's DISCOVERY STUDIO 2.1. Docking is a method which predicts the preferred orientation of one molecule to a second when bound to each other to form a stable complex. Out of 13 compounds characterized from Pseudarthria viscida, only one of them docked with Tumour necrosis factor α.

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Section: Resultsmentioning

confidence: 99%

In Silico analysis of compounds characterized fromPseudarthria viscida root with TNF

Rajan¹

2012

J. App. Pharm. Sci.

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“…All the docking studies were carried out by default setting of the LibDock software and then the generated results of these docking studies were subjected to the "Score Ligand Poses" built-in function of the Discovery Studio to evaluate and rank the docking results. The best pose of each docking study was chosen based on the LigScore2 (35). Furthermore, the best pose of each docking study was energy minimized with the protein structure by the "Ligand Minimization" function of the Discovery Studio.…”

Section: Three-dimension Modelingmentioning

confidence: 99%

SIRT Inhibitors Induce Cell Death and p53 Acetylation through Targeting Both SIRT1 and SIRT2

Peck

Chen

et al. 2010

Molecular Cancer Therapeutics

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SIRT proteins play an important role in the survival and drug resistance of tumor cells, especially during chemotherapy. In this study, we investigated the potency, specificity, and cellular targets of three SIRT inhibitors, Sirtinol, Salermide, and EX527. Cell proliferative and cell cycle analyses showed that Sirtinol and Salermide, but not EX527, were effective in inducing cell death at concentrations of 50 μmol/L or over in MCF-7 cells. Instead, EX527 caused cell cycle arrest at G 1 at comparable concentrations. In vitro SIRT assays using a p53 peptide substrate showed that all three compounds are potent SIRT1/2 inhibitors, with EX527 having the highest inhibitory activity for SIRT1. Computational docking analysis showed that Sirtinol and Salermide have high degrees of selectivity for SIRT1/2, whereas EX527 has high specificity for SIRT1 but not SIRT2. Consistently, Sirtinol and Salermide, but not EX527, treatment resulted in the in vivo acetylation of the SIRT1/2 target p53 and SIRT2 target tubulin in MCF-7 cells, suggesting that EX527 is ineffective in inhibiting SIRT2 and that p53 mediates the cytotoxic function of Sirtinol and Salermide. Studies using breast carcinoma cell lines and p53-deficient mouse fibroblasts confirmed that p53 is essential for the Sirtinol and Salermideinduced apoptosis. Further, we showed using small interfering RNA that silencing both SIRTs, but not SIRT1 and SIRT2 individually, can induce cell death in MCF-7 cells. Together, our results identify the specificity and cellular targets of these novel inhibitors and suggest that SIRT inhibitors require combined targeting of both SIRT1 and SIRT2 to induce p53 acetylation and cell death. Mol Cancer Ther; 9(4); 844-55. ©2010 AACR.

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“…30 The obtained poses were subsequently scored using the LigScore scoring function. 31 The best pose was then energy minimized with CHARMm 32 allowing full flexibility for the ligand and only side-chain flexibility for the receptor. All calculations were carried out in the Discovery Studio 1.2 environment (Accelrys, Inc.) as previously described.…”

Section: Targeting Therapy For Breast Carcinoma Research Articlesmentioning

confidence: 99%

Targeting Therapy for Breast Carcinoma by ATP Synthase Inhibitor Aurovertin B

et al. 2008

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Targeting of tumor tissues is one of the most powerful approaches to accelerate the efficiency of anticancer treatments. The investigation of effective targets, including proteins specifically and abundantly expressed in abnormal regions, has been one of the most important research topics in cancer therapy. In this study, we performed a proteomic analysis on human breast carcinoma tissues to investigate the tumor-specific protein expression in breast carcinoma. Our study showed that ATP synthase was up-regulated in tumor tissues and was present on the plasma membrane of breast cancer cells. Furthermore, we treated the breast cancer cells with ATP synthase inhibitors and examined the inhibitory efficiency. Aurovertin B, an ATP synthase inhibitor, has strong inhibition on the proliferation of several breast cancer cell lines, but little influence on the normal cell line MCF-10A. Aurovertin B inhibits proliferation of breast cancer cells by inducing apoptosis and arresting cell cycle at the G0/G1 phase. This study showed aurovertin B can be used as an antitumorigenic agent and may be exploited in cancer chemotherapy.

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LigScore: a novel scoring function for predicting binding affinities

Cited by 350 publications

References 43 publications

In Silico analysis of compounds characterized fromPseudarthria viscida root with TNF

In Silico analysis of compounds characterized fromPseudarthria viscida root with TNF

SIRT Inhibitors Induce Cell Death and p53 Acetylation through Targeting Both SIRT1 and SIRT2

Targeting Therapy for Breast Carcinoma by ATP Synthase Inhibitor Aurovertin B

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