Ultrahigh specificity in a network of computationally designed protein-interaction pairs

Ravit Netzer, Dina Listov, Rosalie Lipsh, Orly Dym, Shira Albeck, Orli Knop, Colin Kleanthous and Sarel J. Fleishman ()
Additional contact information
Ravit Netzer: Weizmann Institute of Science
Dina Listov: Weizmann Institute of Science
Rosalie Lipsh: Weizmann Institute of Science
Orly Dym: Weizmann Institute of Science
Shira Albeck: Weizmann Institute of Science
Orli Knop: Weizmann Institute of Science
Colin Kleanthous: University of Oxford, South Parks Road
Sarel J. Fleishman: Weizmann Institute of Science

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract Protein networks in all organisms comprise homologous interacting pairs. In these networks, some proteins are specific, interacting with one or a few binding partners, whereas others are multispecific and bind a range of targets. We describe an algorithm that starts from an interacting pair and designs dozens of new pairs with diverse backbone conformations at the binding site as well as new binding orientations and sequences. Applied to a high-affinity bacterial pair, the algorithm results in 18 new ones, with cognate affinities from pico- to micromolar. Three pairs exhibit 3-5 orders of magnitude switch in specificity relative to the wild type, whereas others are multispecific, collectively forming a protein-interaction network. Crystallographic analysis confirms design accuracy, including in new backbones and polar interactions. Preorganized polar interaction networks are responsible for high specificity, thus defining design principles that can be applied to program synthetic cellular interaction networks of desired affinity and specificity.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-07722-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07722-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-07722-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().