"Comparative Analysis of Linker Design in Protein Fusion Inhibitors for Enhanced Binding Flexibility"
DOI:
https://doi.org/10.53555/jaz.v44i2.5044Keywords:
GGGS linkers, Happy_06, fusion proteins, linker length, molecular dynamics.Abstract
This study investigates the impact of linker length on the flexibility and binding efficiency of protein fusion inhibitors targeting viral proteins. Fusion proteins play a critical role in developing antiviral therapeutics, and the design of peptide linkers is crucial in optimizing their performance. We designed a series of fusion proteins, ranging from Happy_00 (no linker) to Happy_10 (ten GGGS linkers), to analyze how varying linker lengths influence binding stability and flexibility. Molecular docking simulations provided insights into binding energies, revealing that Happy_06, with six GGGS linkers, exhibited enhanced binding affinity due to increased flexibility at the target site. Structural analyses, including Ramachandran plots, indicated favorable conformational stability for Happy_06 compared to Happy_00. Solvent accessibility assessments demonstrated that longer linkers improve the protein's ability to interact with deeper or more complex binding sites. The findings suggest that optimizing linker design is essential for improving the efficacy of protein fusion inhibitors, particularly in targeting secondary cleavage sites in viral proteins. This study contributes to a better understanding of protein fusion design, paving the way for the development of more effective antiviral therapeutics.
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Copyright (c) 2023 Mohan Kumar B. S., Sethupathi Raj S., Kumar, Shalini K.S., V. N. Narasimha Murthy, Rudresh Kumar K.J.
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