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BioAssay: AID 32788

Binding affinity against Adipocyte lipid binding protein

The prediction of the binding affinity between a protein and ligands is one of the most challenging issues for computational biochemistry and drug discovery. While the enthalpic contribution to binding is routinely available with molecular mechanics methods, the entropic contribution is more difficult to estimate. We describe and apply a relatively simple and intuitive calculation procedure for more ..
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 Tested Compounds
 Tested Compounds
All(4)
 
 
Active(1)
 
 
Unspecified(3)
 
 
 Tested Substances
 Tested Substances
All(4)
 
 
Active(1)
 
 
Unspecified(3)
 
 
 Related BioAssays
 Related BioAssays
AID: 32788
Data Source: ChEMBL (29917)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-24
Modify Date: 2014-08-24

Data Table ( Complete ):           View Active Data    View All Data
BioActive Compound: 1
Description:
Title: Simple, intuitive calculations of free energy of binding for protein-ligand complexes. 1. Models without explicit constrained water.

Abstract: The prediction of the binding affinity between a protein and ligands is one of the most challenging issues for computational biochemistry and drug discovery. While the enthalpic contribution to binding is routinely available with molecular mechanics methods, the entropic contribution is more difficult to estimate. We describe and apply a relatively simple and intuitive calculation procedure for estimating the free energy of binding for 53 protein-ligand complexes formed by 17 proteins of known three-dimensional structure and characterized by different active site polarity. HINT, a software model based on experimental LogP(o/w) values for small organic molecules, was used to evaluate and score all atom-atom hydropathic interactions between the protein and the ligands. These total scores (H(TOTAL)), which have been previously shown to correlate with DeltaG(interaction) for protein-protein interactions, correlate with DeltaG(binding) for protein-ligand complexes in the present study with a standard error of +/-2.6 kcal mol(-1) from the equation DeltaG(binding) = -0.001 95 H(TOTAL) - 5.543. A more sophisticated model, utilizing categorized (by interaction class) HINT scores, produces a superior standard error of +/-1.8 kcal mol(-1). It is shown that within families of ligands for the same protein binding site, better models can be obtained with standard errors approaching +/-1.0 kcal mol(-1). Standardized methods for preparing crystallographic models for hydropathic analysis are also described. Particular attention is paid to the relationship between the ionization state of the ligands and the pH conditions under which the binding measurements are made. Sources and potential remedies of experimental and modeling errors affecting prediction of DeltaG(binding) are discussed.
(PMID: 12036355)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Putative Target:

ChEMBL Target ID: 10189
Target Type: SINGLE PROTEIN
Pref Name: Fatty acid binding protein adipocyte
Synonyms: A-FABP;Adipocyte lipid-binding protein;Adipocyte-type fatty acid-binding protein;AFABP;ALBP;Fatty acid-binding protein 4;Fatty acid-binding protein; adipocyte;
Gene Name: FABP4;
Protein Accession: P15090;
Protein GI: 119781;
Organism: Homo sapiens
Tax ID: 9606
Target Classification: auxiliary transport protein fabp
Confidence: Homologous single protein target assigned
Relationship Type: Homologous protein target assigned
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: Binding
Assay Data Source: Scientific Literature
Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Kd*Kd PubChem standard valueFloatμM
3BEIBinding Efficiency Index(nM)Float
2SEISurface Efficiency Index(nM)Float
4LELigand EfficiencyFloat
5LLELipophilic Ligand EfficiencyFloat
6Kd activity commentKd activity commentString
7Kd standard flagKd standard flagInteger
8Kd qualifierKd qualifierString
9Kd published valueKd published valueFloatμM
10Kd standard valueKd standard valueFloatnM

* Activity Concentration.

Data Table (Concise)
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