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Published on: December 1, 2020
SMAP-WS: a parallel web service for structural proteome-wide ligand-binding site comparison
Jingyuan Ren1, Lei Xie, Wilfred W Li
1San Diego Supercomputer Center, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Nucleic Acids Research
|May 21, 2010
Summary
The SMAP web service (SMAP-WS) identifies similar protein ligand-binding sites using advanced algorithms for drug discovery. This tool aids in predicting drug side effects and repurposing medications, advancing biological and drug development research.
Area of Science:
- Computational Biology
- Structural Bioinformatics
- Drug Discovery
Background:
- Protein ligand-binding site analysis is crucial for understanding protein structure, function, evolution, and therapeutic development.
- Existing methods for proteome-wide analysis of binding sites are limited.
- Identifying functional and evolutionary relationships across protein folds is challenging.
Purpose of the Study:
- To introduce the SMAP web service (SMAP-WS) for large-scale 3D ligand-binding site comparison and similarity searching.
- To provide a tool for predicting ligand-binding pockets and identifying functional/evolutionary relationships.
- To facilitate drug discovery through prediction of side effects and drug repurposing.
Main Methods:
- SMAP-WS utilizes a shape descriptor, the Geometric Potential, to characterize protein structures and predict ligand-binding pockets.
- A sequence order independent profile-profile alignment (SOIPPA) algorithm detects and aligns similar pockets.
- An extreme value distribution model assesses the statistical significance of alignment matches.
Main Results:
- SMAP-WS algorithms have been benchmarked and demonstrate superior performance compared to existing methods.
- Experimental validation has confirmed several predictions made by SMAP-WS.
- The service has been successfully applied to predict drug side effects and repurpose existing drugs.
Conclusions:
- SMAP-WS offers a powerful, validated platform for proteome-wide analysis of ligand-binding sites.
- The web service and API support diverse research questions in biology and drug discovery.
- SMAP-WS advances the understanding of protein interactions and accelerates therapeutic development.
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