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08:31
Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
Published on: December 1, 2020
Specificity quantification of biomolecular recognition and its implication for drug discovery
1Department of Chemistry & Physics, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, USA.
Scientific Reports
|March 14, 2012
Summary
We developed a novel method, SPecificity and Affinity (SPA), to quantify both binding affinity and specificity in biomolecular recognition. SPA outperforms existing methods in predicting binding affinity and native binding pose for drug discovery.
Area of Science:
- Computational chemistry
- Structural biology
- Drug discovery
Background:
- Biomolecular recognition relies on both affinity and specificity.
- Existing quantitative methods primarily focus on affinity, neglecting specificity quantification.
Purpose of the Study:
- To develop a novel method, SPecificity and Affinity (SPA), for simultaneously optimizing quantified specificity and affinity prediction.
- To address the lack of specificity quantification in previous biomolecular recognition models.
Main Methods:
- Developed the SPA method based on funneled energy landscape theory.
- Simultaneously optimized specificity (discriminating native vs. non-native binding) and affinity.
- Benchmarked SPA against 16 other scoring functions.
Main Results:
- SPA demonstrated superior performance in predicting binding affinity and native binding pose compared to 16 other methods.
- SPA successfully discriminated between selective and non-selective drugs for the COX-2 target.
- The method showed significant potential in identifying lead compounds.
Conclusions:
- SPA offers a robust approach for quantifying both specificity and affinity in biomolecular recognition.
- The method shows promise for enhancing lead compound identification in drug discovery.
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