Characterizing the Hot Spots Involved in RON-MSPβ Complex Formation Using In Silico Alanine Scanning Mutagenesis and Molecular Dynamics Simulation

Advanced Pharmaceutical Bulletin
Omid ZareiSiavoush Dastmalchi

Abstract

Purpose: Implication of protein-protein interactions (PPIs) in development of many diseases such as cancer makes them attractive for therapeutic intervention and rational drug design. RON (Recepteur d'Origine Nantais) tyrosine kinase receptor has gained considerable attention as promising target in cancer therapy. The activation of RON via its ligand, macrophage stimulation protein (MSP) is the most common mechanism of activation for this receptor. The aim of the current study was to perform in silico alanine scanning mutagenesis and to calculate binding energy for prediction of hot spots in protein-protein interface between RON and MSPβ chain (MSPβ). Methods: In this work the residues at the interface of RON-MSPβ complex were mutated to alanine and then molecular dynamics simulation was used to calculate binding free energy. Results: The results revealed that Gln(193), Arg(220), Glu(287), Pro(288), Glu(289), and His(424) residues from RON and Arg(521), His(528), Ser(565), Glu(658), and Arg(683) from MSPβ may play important roles in protein-protein interaction between RON and MSP. Conclusion: Identification of these RON hot spots is important in designing anti-RON drugs when the aim is to disrupt RON-MSP interaction. In the sam...Continue Reading

Citations

May 3, 2019·PloS One·Karolina PlösslUlrike Friedrich
Nov 30, 2018·BMC Bioinformatics·Quanya LiuJinyan Li

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Methods Mentioned

BETA
X-ray
NMR
in silico methods
pharmacotherapy

Software Mentioned

AMBER
Centus
Linux
Pdb Viewer ( DeepView )
Assisted Model Building with Energy Refinement ( AMBER )
GBSA
Swiss
MM

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