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Computational modeling and validation of the alpha chain of macrophage stimulating protein
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Asrin Rashidi1    , Hadi Mohammadi2 , Bayazid Ghaderi2 , Omid Zarei3 |
1- Ph.D. in Molecular Medicine, Department of Pediatrics, Besat Hospital, Kurdistan University of Medical Sciences, Sanandaj, Iran
2- Associate Professor, Cancer and Immunology Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
3- Assistant Professor, Cancer and Immunology Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran , o.zarei@muk.ac.ir |
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Abstract: (194 Views) |
Background and Aim: The receptor tyrosine kinase RON plays important roles in various biological processes, including cell proliferation, migration, and survival, and its dysregulation has been associated with various types of cancer. Macrophage-stimulating protein (MSP) consists of alpha and beta chains and activates RON upon binding. Despite structural studies on MSP, complete experimental structural information on its alpha chain is not available. This study aimed to model and validate the MSP alpha chain structure and the structure of mature MSP.
Materials and Methods: Models 1-3 of the MSP alpha chain were generated using SWISS-MODEL, I-TASSER, and AlphaFold. The mature MSP sequence, comprising amino acids 19–711, was modeled as a continuous sequence using AlphaFold to generate Model 4. The models were validated using Verify3D, PROCHECK, and ERRAT.
Results: In Models 1-3, 81.32%, 86.88%, and 82.58% of the amino acid residues, respectively, had 3D-1D scores of ≥0.1, while this value was 79.37% for Model 4. According to the Ramachandran plots, 86.0%, 65.4%, and 84.5% of the residues in Models 1–3, respectively, were located in the most favored regions, compared to 88.2% in Model 4. No residues were located in the disallowed region. The ERRAT score for Model 4 was 93.15.
Conclusion: Modeling of MSP, particularly Model 4, provides more comprehensive coverage of the mature protein and may serve as a basis for future structural and computational studies of MSP and RON. Experimental validation of the MSP structure is necessary to complement the structural information obtained through computational modeling. |
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| Keywords: Cancer, Computational modeling, Macrophage-stimulating protein (MSP), RON receptor, Three-dimensional protein structure |
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Full-Text [PDF 1724 kb]
(103 Downloads)
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Type of Study: Original Research |
Subject:
Molecular Medicine and Genetics
Received: 2023/09/7 | Accepted: 2024/01/17 | Published: 2026/09/26
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