Prediction of estrogen receptor β ligands potency and selectivity by docking and MM-GBSA scoring methods using three different scaffolds

Balaji, B.; Ramanathan, Meena

doi:10.3109/14756366.2011.618990

Cited by 20 publications

(11 citation statements)

References 20 publications

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“…The calculated relative ΔG bind values against pIC 50 (Table S3) are plotted in Figure 4A. The implemented computational protocol (docking + MM-GBSA) has been successfully used in SAR studies of a given compound series against specific targets [21,25,26,27]. A low correlation coefficient was obtained for the study done against the T3tre1CC model ( R 2 = 0.491) and moderate correlation coefficients (T3twiOO: R 2 = 0.687 and T3tre2OO: R 2 = 0.753) were obtained against TASK-3 models with open fenestrations.…”

Section: Resultsmentioning

confidence: 99%

Structure/Activity Analysis of TASK-3 Channel Antagonists Based on a 5,6,7,8 tetrahydropyrido[4,3-d]pyrimidine

Ramírez

Bedoya

Kiper

et al. 2019

IJMS

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TASK-3 potassium (K+) channels are highly expressed in the central nervous system, regulating the membrane potential of excitable cells. TASK-3 is involved in neurotransmitter action and has been identified as an oncogenic K+ channel. For this reason, the understanding of the action mechanism of pharmacological modulators of these channels is essential to obtain new therapeutic strategies. In this study we describe the binding mode of the potent antagonist PK-THPP into the TASK-3 channel. PK-THPP blocks TASK-1, the closest relative channel of TASK-3, with almost nine-times less potency. Our results confirm that the binding is influenced by the fenestrations state of TASK-3 channels and occurs when they are open. The binding is mainly governed by hydrophobic contacts between the blocker and the residues of the binding site. These interactions occur not only for PK-THPP, but also for the antagonist series based on 5,6,7,8 tetrahydropyrido[4,3-d]pyrimidine scaffold (THPP series). However, the marked difference in the potency of THPP series compounds such as 20b, 21, 22 and 23 (PK-THPP) respect to compounds such as 17b, inhibiting TASK-3 channels in the micromolar range is due to the presence of a hydrogen bond acceptor group that can establish interactions with the threonines of the selectivity filter.

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Section: Resultsmentioning

confidence: 99%

Structure/Activity Analysis of TASK-3 Channel Antagonists Based on a 5,6,7,8 tetrahydropyrido[4,3-d]pyrimidine

Ramírez

Bedoya

Kiper

et al. 2019

IJMS

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“…Molecular mechanics -Generalized Born solvent accessibility (MM-GBSA) method was used to calculate enthalpy for the formation of complex, number of HBs and relative change in binding free energy are conducted to deeply explore the molecular basis for the binding of complex system with screened molecules. The MM-GBSA method is based on end point method and it is efficient, reliable and broadly used to calculate accurate relative change in binding free energies (Al-Anazi et al, 2018;Balaji & Ramanathan, 2012). This method combines the Generalized Born (GB) electrostatics with molecular mechanics (MM) and solvent accessibility (SA) models or continuum solvent approaches, to estimate binding energies.…”

Section: Relative Change In Binding Free Energy Calculationsmentioning

confidence: 99%

Promising inhibitors of main protease of novel corona virus to prevent the spread of COVID-19 using docking and molecular dynamics simulation

Kumar

Kumari

Vishvakarma

et al. 2020

Journal of Biomolecular Structure and Dynamics

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Coronavirus disease-2019 (COVID-19) is a global health emergency and the matter of serious concern, which has been declared a pandemic by WHO. Till date, no potential medicine/ drug is available to cure the infected persons from SARS-CoV-2. This deadly virus is named as novel 2019-nCoV coronavirus and caused coronavirus disease, that is, COVID-19. The first case of SARS-CoV-2 infection in human was confirmed in the Wuhan city of the China. COVID-19 is an infectious disease and spread from man to man as well as surface to man . In the present work, in silico approach was followed to find potential molecule to control this infection. Authors have screened more than one million molecules available in the ZINC database and taken the best two compounds based on binding energy score. These lead molecules were further studied through docking against the main protease of SARS-CoV-2. Then, molecular dynamics simulations of the main protease with and without screened compounds were performed at room temperature to determine the thermodynamic parameters to understand the inhibition. Further, molecular dynamics simulations at different temperatures were performed to understand the efficiency of the inhibition of the main protease in the presence of the screened compounds. Change in energy for the formation of the complexes between the main protease of novel coronavirus and ZINC20601870 as well ZINC00793735 at room temperature was determined on applying MM-GBSA calculations. Docking and molecular dynamics simulations showed their antiviral potential and may inhibit viral replication experimentally.

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“…Six selected compounds with the highest minimum docking scores, annotated with their marketing approval status, indications, most frequently observed side effects, minimum docking score, and average docking score. Docking scores provide a rough estimation of binding energy ( kcal/mol) G, Δ [27,28]. Lower scores indicate higher binding affinity.…”

Section: Resultsmentioning

confidence: 99%

Homology Modeling of TMPRSS2 Yields Candidate Drugs That May Inhibit Entry of SARS-CoV-2 into Human Cells

Rensi

Russ²,

Liu³

et al. 2020

Preprint

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The most rapid path to discovering treatment options for the novel coronavirus SARS-CoV-2 is to find existing medications that are active against the virus. We have focused on identifying repurposing candidates for the transmembrane serine protease family member II (TMPRSS2), which is critical for entry of coronaviruses into cells. Using known 3D structures of close homologs, we created seven homology models. We also identified a set of serine protease inhibitor drugs, generated several conformations of each, and docked them into our models. We used three known chemical (non-drug) inhibitors and one validated inhibitor of TMPRSS2 in MERS as benchmark compounds and found six compounds with predicted high binding affinity in the range of the known inhibitors. We also showed that a previously published weak inhibitor, Camostat, had a significantly lower binding score than our six compounds. All six compounds are anticoagulants with significant and potentially dangerous clinical effects and side effects. Nonetheless, if these compounds significantly inhibit SARS-CoV-2 infection, they could represent a potentially useful clinical tool.

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Prediction of estrogen receptor β ligands potency and selectivity by docking and MM-GBSA scoring methods using three different scaffolds

Cited by 20 publications

References 20 publications

Structure/Activity Analysis of TASK-3 Channel Antagonists Based on a 5,6,7,8 tetrahydropyrido[4,3-d]pyrimidine

Structure/Activity Analysis of TASK-3 Channel Antagonists Based on a 5,6,7,8 tetrahydropyrido[4,3-d]pyrimidine

Promising inhibitors of main protease of novel corona virus to prevent the spread of COVID-19 using docking and molecular dynamics simulation

Homology Modeling of TMPRSS2 Yields Candidate Drugs That May Inhibit Entry of SARS-CoV-2 into Human Cells

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