ArticleProteins2009
In pursuit of virtual lead optimization: pruning ensembles of receptor structures for increased efficiency and accuracy during docking.
Article in Proteins, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Structural Insights into Neonicotinoids and N-Unsubstituted Metabolites on Human nAChRs by Molecular Docking, Dynamics Simulations, and Calcium Imaging.International journal of molecular sciences · 2023Article
- A Multi-scale Computational Platform to Mechanistically Assess the Effect of Genetic Variation on Drug Responses in Human Erythrocyte Metabolism.PLoS computational biology · 2016Article
- Knowledge-Based Methods To Train and Optimize Virtual Screening Ensembles.Journal of chemical information and modeling · 2016Article
- Induced fit docking, and the use of QM/MM methods in docking.Drug discovery today. Technologies · 2013Review
- Protein flexibility in docking and surface mapping.Quarterly reviews of biophysics · 2012Review
- Utilizing experimental data for reducing ensemble size in flexible-protein docking.Journal of chemical information and modeling · 2012Article
- Efficient incorporation of protein flexibility and dynamics into molecular docking simulations.Biochemistry · 2011Review
- 2,4-Diamino-5-(2'-arylpropargyl)pyrimidine derivatives as new nonclassical antifolates for human dihydrofolate reductase inhibition.Journal of molecular graphics & modelling · 2011Article
- How to choose relevant multiple receptor conformations for virtual screening: a test case of Cdk2 and normal mode analysis.European biophysics journal : EBJ · 2010Article
- Conformational transitions upon ligand binding: holo-structure prediction from apo conformations.PLoS computational biology · 2010Article
- A comparative study of AutoDock and PMF scoring performances, and SAR of 2-substituted pyrazolotriazolopyrimidines and 4-substituted pyrazolopyrimidines as potent xanthine oxidase inhibitors.Journal of computer-aided molecular design · 2010Article
- Scoring ensembles of docked protein:ligand interactions for virtual lead optimization.Journal of chemical information and modeling · 2009Article
- Structure-based approach to the development of potent and selective inhibitors of dihydrofolate reductase from cryptosporidium.Journal of medicinal chemistry · 2008Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Representing receptors as ensembles of protein conformations during docking is a powerful method to approximate protein flexibility and increase the accuracy of the resulting ranked list of compounds. Unfortunately, docking compounds against a large number of ensemble members can increase computational cost and time investment. In this article, we present an efficient method to evaluate and select the most contributive ensemble members prior to docking for targets with a conserved core of residues that bind a ligand moiety. We observed that ensemble members that preserve the geometry of the active site core are most likely to place ligands in the active site with a conserved orientation, generally rank ligands correctly and increase interactions with the receptor. A relative distance approach is used to quantify the preservation of the three-dimensional interatomic distances of the conserved ligand-binding atoms and prune large ensembles quickly. In this study, we investigate dihydrofolate reductase as an example of a protein with a conserved core; however, this method for accurately selecting relevant ensemble members a priori can be applied to any system with a conserved ligand-binding core, including HIV-1 protease, kinases, and acetylcholinesterase. Representing a drug target as a pruned ensemble during in silico screening should increase the accuracy and efficiency of high-throughput analyses of lead analogs.
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