Accelerated engineering of ELP-based materials through hybrid biomimetic-de novo predictive molecular design

• Main Authors: Laakko, Timo, Korkealaakso, Antti, Yildirir, Burcu Firatligil, Batys, Piotr, Liljeström, Ville, Hokkanen, Ari, Nonappa, Penttilä, Merja, Laukkanen, Anssi, Miserez, Ali, Södergård, Caj, Mohammadi, Pezhman
• Other Authors: School of Materials Science and Engineering
• Format: Article
• Language: English
• Published: 2024
• Subjects: Engineering; Computational modeling; De novo design
• Online Access: https://hdl.handle.net/10356/180112
• Institution: Nanyang Technological University

Efforts to engineer high-performance protein-based materials inspired by nature have mostly focused on altering naturally occurring sequences to confer the desired functionalities, whereas de novo design lags significantly behind and calls for unconventional innovative approaches. Here, using partially disordered elastin-like polypeptides (ELPs) as initial building blocks this work shows that de novo engineering of protein materials can be accelerated through hybrid biomimetic design, which this work achieves by integrating computational modeling, deep neural network, and recombinant DNA technology. This generalizable approach involves incorporating a series of de novo-designed sequences with α-helical conformation and genetically encoding them into biologically inspired intrinsically disordered repeating motifs. The new ELP variants maintain structural conformation and showed tunable supramolecular self-assembly out of thermal equilibrium with phase behavior in vitro. This work illustrates the effective translation of the predicted molecular designs in structural and functional materials. The proposed methodology can be applied to a broad range of partially disordered biomacromolecules and potentially pave the way toward the discovery of novel structural proteins.