Get started
Work

Data‐Driven Engineering of Thermostable Collagen‐Mimetic Peptoid Triple Helices

Year: 2026
Type: article
Abstract: Collagen-mimetic peptides (CMPs) are engineered molecules designed to replicate the triple-helical structure of natural collagen. A repeating x-y-Gly sequence is the defining motif of CMPs and is critical to their triple-helical structure and stability. Substitutions to the residues occupying the x and y positions present a means to modulate the CMP structure and properties. Peptoid residues-N-substituted glycine derivatives-present an attractive potential substitution due to their thermal stability, proteolytic resistance, biocompatibility, and diverse palette of non-natural side chains, but also tend to introduce a high degree of backbone flexibility that can diminish the stability of the triple helix. In this work, we report a computational active learning cycle comprising molecular dynamics simulation, Gaussian process regression, and Bayesian optimization to computationally identify a number of promising peptoid substitutions predicted to stabilize the desired quaternary structure through side chain interactions and produce stable peptoid-based collagen-like triple helices. To experimentally test the computational predictions, a top candidate identified by the screen was synthesized and imaged using scanning electron microscopy to resolve fibril-like bundles consistent with collagen-like triple helices. This work predicts a number of CMP peptoid substitutions capable of forming stable triple-helical structures, presents a generalizable design strategy for engineering desired peptoid structures, and opens new avenues for the design of peptoid-based biomimetic materials.
DOI: 10.1002/marc.202500917
Authors: Alex Berlaga, Renyu Zheng, Zeqian Zhang, Junhee Lee, Diya Gandhi, Chun‐Long Chen, Andrew L. Ferguson
Language: English
Subfield: Biomaterials
Open Access status: hybrid
Estimated APC paid: $4,550
Funders: National Science Foundation, U.S. Department of Energy, Battelle, Office of Science, Division of Materials Research, Basic Energy Sciences, Pacific Northwest National Laboratory, Energy Frontier Research Centers, National Science Foundation Graduate Research Fellowship Program
Awards: G125460123, G1772167607, G1851334662, G1899721271, G2506945562, G2510423872, G2589448798, G2879087551, G2988778103, MRI: Acquisition of a high-performance GPU-based computer for advanced multiscale materials modeling, G3349933317, Graduate Research Fellowship Program (GRFP), G391136020, CSSAS: THE CENTER FOR THE SCIENCE OF SYNTHESIS ACROSS SCALES, G400111597, G5321382714, CSSAS: THE CENTER FOR THE SCIENCE OF SYNTHESIS ACROSS SCALES, G5653134238, G5726405315, G7560550554, G7820774471, G821644656
OpenAlex ID: W7131436749
FWCI:
Cites:
Cited by:
Related to: