5UP5

Solution structure of the de novo mini protein EHEE_rd1_0284

5UP5 の概要

• エントリーDOI: 10.2210/pdb5up5/pdb
• 関連するPDBエントリー: 5UOI 5UP1
• NMR情報: BMRB: 30242
• 分子名称: EHEE_rd1_0284 (1 entity in total)
• 機能のキーワード: de novo design, mini protein, de novo protein
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4973.37

構造登録者

Houliston, S.,Rocklin, G.J.,Lemak, A.,Carter, L.,Chidyausiku, T.M.,Baker, D.,Arrowsmith, C.H. (登録日: 2017-02-01, 公開日: 2017-07-26, 最終更新日: 2024-05-15)

主引用文献

Rocklin, G.J.,Chidyausiku, T.M.,Goreshnik, I.,Ford, A.,Houliston, S.,Lemak, A.,Carter, L.,Ravichandran, R.,Mulligan, V.K.,Chevalier, A.,Arrowsmith, C.H.,Baker, D.
Global analysis of protein folding using massively parallel design, synthesis, and testing.
Science, 357:168-175, 2017

PubMed Abstract: Proteins fold into unique native structures stabilized by thousands of weak interactions that collectively overcome the entropic cost of folding. Although these forces are "encoded" in the thousands of known protein structures, "decoding" them is challenging because of the complexity of natural proteins that have evolved for function, not stability. We combined computational protein design, next-generation gene synthesis, and a high-throughput protease susceptibility assay to measure folding and stability for more than 15,000 de novo designed miniproteins, 1000 natural proteins, 10,000 point mutants, and 30,000 negative control sequences. This analysis identified more than 2500 stable designed proteins in four basic folds-a number sufficient to enable us to systematically examine how sequence determines folding and stability in uncharted protein space. Iteration between design and experiment increased the design success rate from 6% to 47%, produced stable proteins unlike those found in nature for topologies where design was initially unsuccessful, and revealed subtle contributions to stability as designs became increasingly optimized. Our approach achieves the long-standing goal of a tight feedback cycle between computation and experiment and has the potential to transform computational protein design into a data-driven science.

PubMed: 28706065
DOI: 10.1126/science.aan0693

実験手法

SOLUTION NMR