6W3W

An enumerative algorithm for de novo design of proteins with diverse pocket structures

6W3W の概要

• エントリーDOI: 10.2210/pdb6w3w/pdb
• 分子名称: DENOVO NTF2, NITRATE ION (3 entities in total)
• 機能のキーワード: ntf2, de novo design, de novo protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12811.37

構造登録者

Bera, A.K.,Basanta, B.,Dimaio, F.,Sankaran, B.,Baker, D. (登録日: 2020-03-09, 公開日: 2020-04-08, 最終更新日: 2024-04-03)

主引用文献

Basanta, B.,Bick, M.J.,Bera, A.K.,Norn, C.,Chow, C.M.,Carter, L.P.,Goreshnik, I.,Dimaio, F.,Baker, D.
An enumerative algorithm for de novo design of proteins with diverse pocket structures.
Proc.Natl.Acad.Sci.USA, 117:22135-22145, 2020

PubMed Abstract: To create new enzymes and biosensors from scratch, precise control over the structure of small-molecule binding sites is of paramount importance, but systematically designing arbitrary protein pocket shapes and sizes remains an outstanding challenge. Using the NTF2-like structural superfamily as a model system, we developed an enumerative algorithm for creating a virtually unlimited number of de novo proteins supporting diverse pocket structures. The enumerative algorithm was tested and refined through feedback from two rounds of large-scale experimental testing, involving in total the assembly of synthetic genes encoding 7,896 designs and assessment of their stability on yeast cell surface, detailed biophysical characterization of 64 designs, and crystal structures of 5 designs. The refined algorithm generates proteins that remain folded at high temperatures and exhibit more pocket diversity than naturally occurring NTF2-like proteins. We expect this approach to transform the design of small-molecule sensors and enzymes by enabling the creation of binding and active site geometries much more optimal for specific design challenges than is accessible by repurposing the limited number of naturally occurring NTF2-like proteins.

PubMed: 32839327
DOI: 10.1073/pnas.2005412117

実験手法

X-RAY DIFFRACTION (1.55 Å)