De novo design of membrane transport proteins

Abstract

Membrane transport proteins, which include transporters and channels, are delicate protein machineries that mediate the exchange of a variety of substances across biomembranes. Accumulated structural and functional knowledge allows for the de novo design of transport proteins with new structures that do not exist in nature.Analysis based on these novel proteins provides new insights into the principles that govern protein assembly, conformational change, and substrate recognition. Here, we review the advances in the de novo design of transporters and channels over recent years and highlight the challenges and opportunities in this field.de novo design, ion channel, membrane transport proteins, nanopore, protein design, protein structure, transporter | INTRODUCTIONDe novo protein design explores the whole protein-sequence space, generating new protein sequences that fold into specified threedimensional structures from scratch. 1 Many de novo water-soluble proteins have been designed, 1 and these proteins can function as biosensors, 2 logic gates, 3,4 molecular switches, 5 therapeutics, 6 and self-assembling materials. 7,8 In comparison, the de novo design of

Microbial membrane transport proteins and their biotechnological applications

“…Results from molecular simulations align well with experimental single-channel measurements (Milenkovic et al 2023 ). In addition, knowledge from structural and functional analysis of membrane transport proteins makes de novo design of new ion channels possible (Zhou and Lu 2022 ). By changing amino acid sequences or by combining functional helical barrels, new channels with novel functions can be created (Scott et al 2021 ).…”

Editorial: Special issue Transporter and Channel

“…They highlighted the challenges and opportunities in potential biotechnological applications. 5 In the end, I thank all the authors for their work and great dedication to these comprehensive reviews, which can encourage further research into transporters and channels.…”

“…The authors presented an overview of the history of de novo membrane protein design and characterized the principles of protein assembly, conformational change, and substrate recognition. They highlighted the challenges and opportunities in potential biotechnological applications 5 …”