IC50-to-Ki: a web-based tool for converting IC50 to Ki values for inhibitors of enzyme activity and ligand binding
TLDR
A new web-server tool estimates Ki values from experimentally determined IC50 values for inhibitors of enzymes and of binding reactions between macromolecules and ligands to enable end users to help gauge the quality of the underlying assumptions used in these calculations.Abstract:
A new web-server tool estimates Ki values from experimentally determined IC50 values for inhibitors of enzymes and of binding reactions between macromolecules (e.g. proteins, polynucleic acids) and ligands. This converter was developed to enable end users to help gauge the quality of the underlying assumptions used in these calculations which depend on the type of mechanism of inhibitor action and the concentrations of the interacting molecular species. Additional calculations are performed for nonclassical, tightly bound inhibitors of enzyme-substrate or of macromolecule-ligand systems in which free, rather than total concentrations of the reacting species are required. Required userdefined input values include the total enzyme (or another target molecule) and substrate (or ligand) concentrations, the Km of the enzyme-substrate (or the Kd of the target-ligand) reaction, and the IC50 value. Assumptions and caveats for these calculations are discussed along with examples taken from the literature. The host database for this converter contains kinetic constants and other data for inhibitors of the proteolytic clostridial neurotoxins (http:// botdb.abcc.ncifcrf.gov/toxin/kiConverter.jsp).read more
Citations
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Journal ArticleDOI
Label-Free Measurements of Reaction Kinetics Using a Droplet-Based Optofluidic Device
Zhangming Mao,Feng Guo,Yuliang Xie,Yanhui Zhao,Michael Ian Lapsley,Lin Wang,John D. Mai,Francesco Costanzo,Tony Jun Huang +8 more
TL;DR: An integrated optofluidic system for label-free characterization of reactions in a nanoliter reagent volume by performing potency (IC50) assays of an inhibitor in a TEM-1 β-lactamase (enzyme) and nitrocefin (substrate) system.
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Two hydrophobic residues can determine the specificity of mitogen-activated protein kinase docking interactions.
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TL;DR: It is demonstrated that the short hydrophobic region at the distal end of the D-site plays a critical role in determining the high selectivity of JNK MAPKs for docking sites in their cognate MAPK kinases.
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Interaction between Plectranthus barbatus herbal tea components and acetylcholinesterase: binding and activity studies
TL;DR: FTIR analysis showed that the plant extract components do not interfere with the secondary structure of the enzyme, but decreases the rate of hydrogen-deuterium exchange, possibly by decreasing solvent accessibility in the acetylcholinesterase active gorge.
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Ligand binding and activation properties of the purified bacterial cyclic nucleotide-gated channel SthK.
TL;DR: The functional characteristics of SthK reported here will permit future studies to analyze ligand gating and discrimination in CNG channels and find that the large difference in channel activation by cAMP or cGMP is caused by the efficacy with which each ligand promotes the conformational changes toward the open state.
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Ensemble-Based Virtual Screening Led to the Discovery of New Classes of Potent Tyrosinase Inhibitors
TL;DR: New classes of potent tyrosinase inhibitors identified by enhanced structure-based virtual screening prediction are reported; the enzyme and melanin content assays were also confirmed.
References
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Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction.
TL;DR: The analysis described shows K I does not equal I 50 when competitive inhibition kinetics apply; however, K I is equal to I 50 under conditions of either noncompetitive or uncompetitive kinetics.
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Development and optimization of a binding assay for the XIAP BIR3 domain using fluorescence polarization
Zaneta Nikolovska-Coleska,Renxiao Wang,Xueliang Fang,Hongguang Pan,York Tomita,Peng Li,Peter P. Roller,Krzysztof Krajewski,Naoyuki G. Saito,Jeanne A. Stuckey,Shaomeng Wang +10 more
TL;DR: The development of a homogeneous high-throughput assay based on fluorescence polarization for measuring the binding affinities of small-molecule inhibitors to the BIR3 domain of XIAP and results obtained indicated that the FP-based competitive binding assay performs correctly as designed.
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A linear equation that describes the steady-state kinetics of enzymes and subcellular particles interacting with tightly bound inhibitors.
TL;DR: D dose-response measurements generate a linear plot of inhibitor concentration divided by degree of inhibition against velocity without inhibitor divided by velocity with inhibitor, which indicates that the inhibitors of oxidative phosphorylation, rutamycin and bongkrekic acid, are tightly bound to rat liver mitochondria.
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BRENDA, AMENDA and FRENDA the enzyme information system: new content and tools in 2009
TL;DR: The web service via a SOAP (Simple Object Access Protocol) interface for access to the BRENDA data has been further enhanced and a new search option provides the access to protein-specific data.
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Fluorescence Polarization Competition Assay: The Range of Resolvable Inhibitor Potency Is Limited by the Affinity of the Fluorescent Ligand
TL;DR: The higher the affinity of the fluorescent ligand, the wider the range of inhibitor potency that can be resolved, and an approximate estimate for the low end of inhibitor K(i) values thatCan be resolved is the K(d) value of theorescent ligand.