ArticleJournal of chemical information and modeling2012
Binding conformation of 2-oxoamide inhibitors to group IVA cytosolic phospholipase A2 determined by molecular docking combined with molecular dynamics.
Article in Journal of chemical information and modeling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 20 citations in OpenAlex.
- Membrane Association Allosterically Regulates Phospholipase AAccounts of chemical research · 2022Article
- 1,4-Disubstituted 1International journal of molecular sciences · 2020Article
- Phospholipase ABiochimica et biophysica acta. Molecular and cell biology of lipids · 2019Review
- Small-molecule inhibitors as potential therapeutics and as tools to understand the role of phospholipases ABiochimica et biophysica acta. Molecular and cell biology of lipids · 2019Review
- Review of four major distinct types of human phospholipase AAdvances in biological regulation · 2018Review
- A New Generation of Arachidonic Acid Analogues as Potential Neurological Agent Targeting Cytosolic Phospholipase AScientific reports · 2017Article
- Membrane and inhibitor interactions of intracellular phospholipases A2.Advances in biological regulation · 2016Review
- Membranes serve as allosteric activators of phospholipase A2, enabling it to extract, bind, and hydrolyze phospholipid substrates.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Fluoroketone inhibition of Ca(2+)-independent phospholipase A2 through binding pocket association defined by hydrogen/deuterium exchange and molecular dynamics.Journal of the American Chemical Society · 2013Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The group IVA cytosolic phospholipase A(2) (GIVA cPLA(2)) plays a central role in inflammation. Long chain 2-oxoamides constitute a class of potent GIVA cPLA(2) inhibitors that exhibit potent in vivo anti-inflammatory and analgesic activity. We have now gained insight into the binding of 2-oxoamide inhibitors in the GIVA cPLA(2) active site through a combination of molecular docking calculations and molecular dynamics simulations. Recently, the location of the 2-oxoamide inhibitor AX007 within the active site of the GIVA cPLA(2) was determined using a combination of deuterium exchange mass spectrometry followed by molecular dynamics simulations. After the optimization of the AX007-GIVA cPLA(2) complex using the docking algorithm Surflex-Dock, a series of additional 2-oxoamide inhibitors have been docked in the enzyme active site. The calculated binding affinity presents a good statistical correlation with the experimental inhibitory activity (r(2) = 0.76, N = 11). A molecular dynamics simulation of the docking complex of the most active compound has revealed persistent interactions of the inhibitor with the enzyme active site and proves the stability of the docking complex and the validity of the binding suggested by the docking calculations. The combination of molecular docking calculations and molecular dynamics simulations is useful in defining the binding of small-molecule inhibitors and provides a valuable tool for the design of new compounds with improved inhibitory activity against GIVA cPLA(2).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.