学習された表面指紋によるタンパク質の相互作用のデノボ設計

Pablo Gainza^1,2,3, Sarah Wehrle^1,2, Alexandra Van Hall-Beauvais^1,2

¹Laboratory of Protein Design and Immunoengineering, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

Nature

|April 26, 2023

まとめ

科学者たちは新しいタンパク質結合剤を設計するための新しいディープラーニングの方法を開発しましたこの表面を中心としたアプローチはタンパク質の相互作用を正確に予測し合成生物学と医学の進歩を可能にします

科学分野:

計算生物学
構造生物学
生物化学

背景:

タンパク質同士の相互作用は生物学的プロセスにとって根本的なものです
これらの相互作用の分子決定因子を理解することは極めて重要ですが難しいことです
既存のデータ制限により,ネットワークの総合的な分析や,新しい結合器の設計が困難である.

研究の目的:

タンパク質とタンパク質の相互作用を理解し設計するための新しい計算フレームワークを開発する.
タンパク質の結合体の計算設計に新しいパラダイムを作り出すこと
表面中心のジオメトリック・ディープ・ラーニングの有効性を実証する.

主な方法:

タンパク質の表面で動作するジオメトリック・ディープ・ラーニング・フレームワークを利用した
相互作用の幾何学的および化学的な特徴を捕捉する生成された表面の指紋.
特定の標的 (SARS-CoV-2スパイク,PD-1,PD-L1,CTLA-4) に対して計算的に設計されたデノボタンパク質結合剤.

主要な成果:

標的タンパク質に対するナノモラアフィニティを持つ設計されたタンパク質結合剤
実験的にいくつかのデザインを最適化し,他のものは純粋にシリコで生成されました.
構造と変異の特徴は極めて正確な予測を裏付けました
表面中心的なアプローチは分子認識の決定要因を効果的に捉えます.

結論:

開発されたジオメトリック・ディープ・ラーニング・フレームワークにより,タンパク質の相互作用を新たに設計できます.
このアプローチは合成生物学とトランスレーション医学にとって重要な進歩です
この方法は,望ましい機能を持つ人工タンパク質の作成を容易にする.

さらに関連する動画

10:58

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

Published on: July 25, 2013

17.1K

07:42

In-vivo Detection of Protein-protein Interactions on Micro-patterned Surfaces

Published on: March 19, 2010

10.8K

関連する概念動画

02:04

Protein-protein Interfaces

12.6K

Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...

12.6K

02:04

Protein-Protein Interfaces

3.8K

02:26

Protein Networks

4.0K

An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...

4.0K

01:49

Conserved Binding Sites

4.3K

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...

4.3K

01:24

Protein Organization

6.6K

Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence....

6.6K

02:35

Noncovalent Attractions in Biomolecules

52.1K

Noncovalent attractions are associations within and between molecules that influence the shape and structural stability of complexes. These interactions differ from covalent bonding in that they do not involve sharing of electrons.
Four types of noncovalent interactions are hydrogen bonds, van der Waals forces, ionic bonds, and hydrophobic interactions.
Hydrogen bonding results from the electrostatic attraction of a hydrogen atom covalently bonded to a strong-electronegative atom like oxygen,...