Pharmacophore annotation using extended Hückel theory

Labute, Paul; Kossner, Markus; Ajamian, Alain; Santavy, Martin; Lin, Anna L.

doi:10.1186/1758-2946-6-s1-p54

Cited by 3 publications

(3 citation statements)

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“…68 Pharmacophore modeling was performed using the MOE Ph4 Query tool with the application of Extended Hückel Theory annotation scheme. 69 Consensus pharmacophore features were automatically computed using a default tolerance distance of 1.2 Å from the ligands' atoms and a 50% threshold of overlapping features. Features were then selected based on visual inspection of known actives in complex with Mpro.…”

Section: Methodsmentioning

confidence: 99%

“…The protein sequences were aligned and superimposed on the pocket residues of the reference compound X77 in Molecular Operating Environment (MOE) 68 . Pharmacophore modeling was performed using the MOE Ph4 Query tool with the application of Extended Hückel Theory annotation scheme 69 . Consensus pharmacophore features were automatically computed using a default tolerance distance of 1.2 Å from the ligands' atoms and a 50% threshold of overlapping features.…”

Section: Pharmacophore Modelingmentioning

confidence: 99%

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Automated discovery of noncovalent inhibitors of SARS-CoV-2 main protease by consensus Deep Docking of 40 billion small molecules

et al. 2021

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Section: Methodsmentioning

confidence: 99%

Section: Pharmacophore Modelingmentioning

confidence: 99%

Automated discovery of noncovalent inhibitors of SARS-CoV-2 main protease by consensus Deep Docking of 40 billion small molecules

et al. 2021

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“…The quality of a structure-based pharmacophore model highly depends on the fidelity of the crystal structure and accuracy of the annotation scheme used for the recognition of molecular features. 23,24 In the present study, we used the "unified" annotation scheme implemented in MOE to develop pharmacophore models.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Exploring Novel N-Myristoyltransferase Inhibitors: A Molecular Dynamics Simulation Approach

et al. 2019

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N -Myristoyltransferase (NMT) is a cytosolic monomeric enzyme involved in the allocation of the myristoyl group to the aminoterminal of glycine in several viral and eukaryotic cellular proteins. NMT has been validated as a potential drug target against kinetoplastid for parasitic protozoa. A multistep virtual screening protocol based on the pharmacophore modeling, molecular docking, and molecular dynamics simulation was carried out. Initially, Maybridge database was virtually screened via a validated pharmacophore model. The effective pharmacophore models were accompanied with exclusion volumes to improve their receiver operating characteristic curve to identify potential NMT inhibitors. The hits identified as actives based on the 3D-pharmacophore model were evaluated by molecular docking studies. In stepwise screening, six compounds were shortlisted for the dynamic simulation to get insights into their binding mode. In conclusion, this study provides fundamental information about the architecture of the binding site and some crucial residues that may provide insights into the development of new antiparasitic agents.

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Insights into the molecular properties underlying antibacterial activity of prenylated (iso)flavonoids against MRSA

Kalli

Araya‐Cloutier

Hageman

et al. 2021

Sci Rep

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High resistance towards traditional antibiotics has urged the development of new, natural therapeutics against methicillin-resistant Staphylococcus aureus (MRSA). Prenylated (iso)flavonoids, present mainly in the Fabaceae, can serve as promising candidates. Herein, the anti-MRSA properties of 23 prenylated (iso)flavonoids were assessed in-vitro. The di-prenylated (iso)flavonoids, glabrol (flavanone) and 6,8-diprenyl genistein (isoflavone), together with the mono-prenylated, 4′-O-methyl glabridin (isoflavan), were the most active anti-MRSA compounds (Minimum Inhibitory Concentrations (MIC) ≤ 10 µg/mL, 30 µM). The in-house activity data was complemented with literature data to yield an extended, curated dataset of 67 molecules for the development of robust in-silico prediction models. A QSAR model having a good fit (R2adj 0.61), low average prediction errors and a good predictive power (Q2) for the training (4% and Q2LOO 0.57, respectively) and the test set (5% and Q2test 0.75, respectively) was obtained. Furthermore, the model predicted well the activity of an external validation set (on average 5% prediction errors), as well as the level of activity (low, moderate, high) of prenylated (iso)flavonoids against other Gram-positive bacteria. For the first time, the importance of formal charge, besides hydrophobic volume and hydrogen-bonding, in the anti-MRSA activity was highlighted, thereby suggesting potentially different modes of action of the different prenylated (iso)flavonoids.

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Pharmacophore annotation using extended Hückel theory

Cited by 3 publications

References 0 publications

Automated discovery of noncovalent inhibitors of SARS-CoV-2 main protease by consensus Deep Docking of 40 billion small molecules

Automated discovery of noncovalent inhibitors of SARS-CoV-2 main protease by consensus Deep Docking of 40 billion small molecules

Exploring Novel N-Myristoyltransferase Inhibitors: A Molecular Dynamics Simulation Approach

Insights into the molecular properties underlying antibacterial activity of prenylated (iso)flavonoids against MRSA

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