Applied Sciences (Mar 2023)

Designing Collagen-Binding Peptide with Enhanced Properties Using Hydropathic Free Energy Predictions

  • Kyle Boone,
  • Aya Kirahm Cloyd,
  • Emina Derakovic,
  • Paulette Spencer,
  • Candan Tamerler

DOI
https://doi.org/10.3390/app13053342
Journal volume & issue
Vol. 13, no. 5
p. 3342

Abstract

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Collagen is fundamental to a vast diversity of health functions and potential therapeutics. Short peptides targeting collagen are attractive for designing modular systems for site-specific delivery of bioactive agents. Characterization of peptide–protein binding involves a larger number of potential interactions that require screening methods to target physiological conditions. We build a hydropathy-based free energy estimation tool which allows quick evaluation of peptides binding to collagen. Previous studies showed that pH plays a significant role in collagen structure and stability. Our design tool enables probing peptides for their collagen-binding property across multiple pH conditions. We explored binding features of currently known collagen-binding peptides, collagen type I alpha chain 2 sense peptide (TKKTLRT) and decorin LRR-10 (LRELHLNNN). Based on these analyzes, we engineered a collagen-binding peptide with enhanced properties across a large pH range in contrast to LRR-10 pH dependence. To validate our predictions, we used a quantum-dots-based binding assay to compare the coverage of the peptides on type I collagen. The predicted peptide resulted in improved collagen binding. Hydropathy of the peptide–protein pair is a promising approach to finding compatible pairings with minimal use of computational resources, and our method allows for quick evaluation of peptides for binding to other proteins. Overall, the free-energy-based tool provides an alternative computational screening approach that impacts protein interaction search methods.

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