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PIIMS Server: A Web Server for Mutation Hotspot Scanning at the Protein-Protein Interface.
Feng-Xu Wu1,2, Jing-Fang Yang1,2, Long-Can Mei1,2
1Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, P. R. China.
Journal of Chemical Information and Modeling
|January 5, 2021
Summary
Researchers developed PIIMS, a free web server for analyzing mutation hotspots in protein-protein interactions (PPIs). PIIMS uses simulations to predict how mutations affect PPI binding free energy, aiding biological pathway understanding.
Area of Science:
- Biochemistry
- Computational Biology
- Structural Biology
Background:
- Protein-protein interactions (PPIs) are crucial for cellular functions and signaling pathways.
- Hotspots are key residues at PPI interfaces significantly impacting binding affinity.
- Understanding mutational effects on hotspots is vital for deciphering protein association mechanisms.
Purpose of the Study:
- To introduce PIIMS, a novel, free web server for comprehensive analysis of mutation hotspots in PPIs.
- To provide a tool that integrates molecular dynamics simulation and free energy perturbation for evaluating hotspot mutations.
- To address the scarcity of tools offering extensive mutational scanning at PPI hotspots.
Main Methods:
- Development of the PIIMS web server, integrating molecular dynamics (MD) simulation and one-step free energy perturbation (FEP).
- Implementation of two core functions: computational alanine scanning for hotspot identification and full mutation scanning for effect evaluation.
- Rigorous validation using a large dataset of 1,341 mutations across 50 PPIs.
Main Results:
- PIIMS accurately predicts binding free energy changes upon mutation, achieving a correlation coefficient (R) of 0.75.
- The server enables comprehensive evaluation of various mutations at identified hotspot residues.
- Demonstrated capability to analyze a diverse set of 50 protein-protein interactions.
Conclusions:
- PIIMS offers a valuable, free resource for researchers studying the impact of mutations on protein-protein interactions.
- The server's ability to perform full mutation scanning at hotspots provides deeper insights into PPI stability and function.
- PIIMS facilitates a better understanding of the forces governing protein association and the role of specific residues.
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