Erratum to: Probing the bradycardic drug binding receptor of HCN-encoded pacemaker channels

Piperacillip (PIP) is b-[D(-)-α-(4-ethy1-2,3-dioxo-l-piperzinylcar-bonylamino)-α-phenylacetamido]-penicillanate. The broad spectrum semisynthetic β-lactam antibiotic is believed to effect bactericidal activity through its affinity for penicillin-binding proteins (PBPs), enzymes on the bacterial cytoplasmic membrane that control elongation and septation during cell growth and division. The purpose of this study was to correlate penetration and binding of 14C-PIP in bacterial cells with drug-induced lethal changes assessed by microscopic, microbiologic and biochemical methods.The bacteria used were clinical isolates of Escherichia coli and Pseudomonas aeruginosa (Figure 1). Sensitivity to the drug was determined by serial tube dilution in Trypticase Soy Broth (BBL) at an inoculum of 104 organisms/ml; the minimum inhibitory concentration of piperacillin for both bacteria was 1 μg/ml. To assess drug binding to PBPs, the bacteria were incubated with 14C-PIP (5 μg/0.09 μCi/ml); controls, in drug-free medium.

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F557L – a novel determinant of hERG channel inhibition: allosteric modulation or drug binding?

Intrinsic Activity ◽

10.25006/ia.1.s1-a3.12 ◽

2013 ◽

Vol 1 (Suppl. 1) ◽

pp. A3.12

Author(s):

Priyanka Saxena

Keyword(s):

Allosteric Modulation ◽

Drug Binding ◽

Herg Channel ◽

Channel Inhibition

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Drug Repurposing Studies Targeting SARS-nCoV2: An Ensemble Docking Approach on Drug Target 3C-like Protease (3CLpro)

10.26434/chemrxiv.12228831 ◽

2020 ◽

Author(s):

Shruti Koulgi ◽

Vinod Jani ◽

Mallikarjunachari Uppuladinne ◽

Uddhavesh Sonavane ◽

Asheet Kumar Nath ◽

...

Keyword(s):

Drug Repurposing ◽

Drug Binding ◽

Ensemble Docking ◽

Drug Molecules ◽

Drug Binding Site ◽

Main Protease ◽

Docking Approach ◽

Novel Coronavirus ◽

Markov State Modeling ◽

Viral Polyprotein

The COVID-19 pandemic has been responsible for several deaths worldwide. The causative agent behind this disease is the Severe Acute Respiratory Syndrome – novel Coronavirus 2 (SARS-nCoV2). SARS-nCoV2 belongs to the category of RNA viruses. The main protease, responsible for the cleavage of the viral polyprotein is considered as one of the hot targets for treating COVID-19. Earlier reports suggest the use of HIV anti-viral drugs for targeting the main protease of SARS-CoV, which caused SARS in the year 2002-03. Hence, drug repurposing approach may prove to be useful in targeting the main protease of SARS-nCoV2. The high-resolution crystal structure of 3CLpro (main protease) of SARS-nCoV2 (PDB ID: 6LU7) was used as the target. The Food and Drug Administration (FDA) approved and SWEETLEAD database of drug molecules were screened. The apo form of the main protease was simulated for a cumulative of 150 ns and 10 μs open source simulation data was used, to obtain conformations for ensemble docking. The representative structures for docking were selected using RMSD-based clustering and Markov State Modeling analysis. This ensemble docking approach for main protease helped in exploring the conformational variation in the drug binding site of the main protease leading to efficient binding of more relevant drug molecules. The drugs obtained as best hits from the ensemble docking possessed anti-bacterial and anti-viral properties. Small molecules with these properties may prove to be useful to treat symptoms exhibited in COVID-19. This in-silico ensemble docking approach would support identification of potential candidates for repurposing against COVID-19.

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Faculty Opinions recommendation of Activity-dependent regulation of HCN pacemaker channels by cyclic AMP: signaling through dynamic allosteric coupling.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1009978.145707 ◽

2002 ◽

Author(s):

Gary Yellen

Keyword(s):

Cyclic Amp ◽

Allosteric Coupling ◽

Pacemaker Channels ◽

Activity Dependent ◽

Cyclic Amp Signaling

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Faculty Opinions recommendation of Beyond thermodynamics: drug binding kinetics could influence epidermal growth factor signaling.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1165980.627143 ◽

2009 ◽

Author(s):

Wolfgang Jahnke

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Drug Binding ◽

Binding Kinetics ◽

Growth Factor Signaling ◽

Epidermal Growth Factor Signaling ◽

Epidermal Growth

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Faculty Opinions recommendation of Fluoroquinolone-gyrase-DNA complexes: two modes of drug binding.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718266482.793491547 ◽

2014 ◽

Author(s):

Anthony Maxwell

Keyword(s):

Drug Binding ◽

Dna Complexes

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Faculty Opinions recommendation of Allosteric coupling of drug binding and intracellular signaling in the A2A adenosine receptor.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732378223.793542005 ◽

2018 ◽

Author(s):

Wolfgang Jahnke

Keyword(s):

Adenosine Receptor ◽

Intracellular Signaling ◽

Drug Binding ◽

A2a Adenosine Receptor ◽

Allosteric Coupling

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Drug Design for Protein Kinases and Phosphatases: Flexible-Receptor Docking, Binding Affinity and Specificity, and Drug-Binding Kinetics

Current Pharmaceutical Design ◽

10.2174/1381612811319260006 ◽

2013 ◽

Vol 19 (26) ◽

pp. 4739-4754 ◽

Cited By ~ 14

Author(s):

Chung Wong ◽

Sneha Bairy

Keyword(s):

Drug Design ◽

Protein Kinases ◽

Binding Affinity ◽

Drug Binding ◽

Binding Kinetics

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Use of Molecular Dynamics Simulations in Structure-Based Drug Discovery

Current Pharmaceutical Design ◽

10.2174/1381612825666190903153043 ◽

2019 ◽

Vol 25 (31) ◽

pp. 3339-3349 ◽

Cited By ~ 6

Author(s):

Indrani Bera ◽

Pavan V. Payghan

Keyword(s):

Molecular Dynamics ◽

Drug Discovery ◽

Molecular Dynamics Simulations ◽

Drug Target ◽

Structural Information ◽

Drug Binding ◽

Structure Based Drug Design ◽

Drug Designing ◽

Target Binding ◽

Dynamics Simulations

Background: Traditional drug discovery is a lengthy process which involves a huge amount of resources. Modern-day drug discovers various multidisciplinary approaches amongst which, computational ligand and structure-based drug designing methods contribute significantly. Structure-based drug designing techniques require the knowledge of structural information of drug target and drug-target complexes. Proper understanding of drug-target binding requires the flexibility of both ligand and receptor to be incorporated. Molecular docking refers to the static picture of the drug-target complex(es). Molecular dynamics, on the other hand, introduces flexibility to understand the drug binding process. Objective: The aim of the present study is to provide a systematic review on the usage of molecular dynamics simulations to aid the process of structure-based drug design. Method: This review discussed findings from various research articles and review papers on the use of molecular dynamics in drug discovery. All efforts highlight the practical grounds for which molecular dynamics simulations are used in drug designing program. In summary, various aspects of the use of molecular dynamics simulations that underline the basis of studying drug-target complexes were thoroughly explained. Results: This review is the result of reviewing more than a hundred papers. It summarizes various problems that use molecular dynamics simulations. Conclusion: The findings of this review highlight how molecular dynamics simulations have been successfully implemented to study the structure-function details of specific drug-target complexes. It also identifies the key areas such as stability of drug-target complexes, ligand binding kinetics and identification of allosteric sites which have been elucidated using molecular dynamics simulations.

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