ディープラーニングを用いたルシフェラーゼの新規設計
Andy Hsien-Wei Yeh1,2,3, Christoffer Norn4,5, Yakov Kipnis4,5,6
1Department of Biochemistry, University of Washington, Seattle, WA, USA. hsyeh@ucsc.edu.
Nature
|February 22, 2023
まとめ
研究者は新しい酵素を設計する ディープラーニングの方法を開発し 生物医学的な用途に高度な活性と特異性を持つ 人工ルシフェラスを生み出しました
科学分野:
- 生物化学
- コンピュータ生物学
- タンパク質工学
背景:
- デノボ酵素の設計は,稀なタンパク質構造と複雑な配列構造関係のために,伝統的に制限に直面した.
- 以前の方法は,望ましい触媒機能と特定の基板結合ポケットを持つ酵素を作成するために苦労しました.
研究 の 目的:
- 多様なポケットの形を持つ理想的なタンパク質の構造を作るための ディープラーニングのアプローチを開発する.
- 高触媒活性と基板特異性を有する新種の人工ルシフェラスを設計する.
主な方法:
- 多数の理想化されたタンパク質構造を生成するために ディープラーニング"全家族幻覚"戦略を採用した.
- 合成ルシフェリン基質を標的とする設計された人工ルシフェラーゼ:ディフェニルテラジンと2-デオキシコエレンテラジン.
- 触媒残留物と基板の相互作用の正確な位置づけのための最適化された活性部位幾何学.
主要な成果:
- ディフェニルテラジンと2デオキシコエレンテラジンの両方に選択的酸化化学発光を示す人工ルシフェラーゼを成功裏に設計した.
- 高活性 (kcat/Km = 10^6 M^-1s^-1) と熱安定 (Tm > 95°C) の人工ルシフェラーゼを開発した.
- ネイティブルシフェラーゼと比較して,著しく高い基板特異性を達成した.
結論:
- ディープラーニングによる 幻覚アプローチにより 高活性で特異的な生物触媒をゼロから作ることができます
- このマイルストーンは コンピューティングによる酵素設計を進めており 新しいルシフェラーゼを含む 様々な酵素の生成の道を開いています
- 設計された酵素は,生物医学とバイオテクノロジーにおける応用に広範囲の可能性を秘めています.
さらに関連する動画
10:13A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells
Published on: July 3, 2013
11.2K
07:19Bioluminescent Optogenetics 2.0: Harnessing Bioluminescence to Activate Photosensory Proteins In Vitro and In Vivo
Published on: August 4, 2021
4.7K
関連する概念動画
01:10Lucid Dreaming
807
Lucid dreaming is a unique state of consciousness where an individual realizes they are dreaming while still in the dream. This awareness allows them to manipulate their dream environment consciously. Researchers like Stephen LaBerge have significantly contributed to the understanding of lucid dreams, highlighting that during these dreams, certain areas of the brain, such as the prefrontal cortex, that involve self-awareness and thought evaluation show increased activity.
Studies have shown...
Studies have shown...
807
01:18Introduction to Learning
1.6K
Learning is the process of acquiring knowledge or skills through practice or experience, leading to long-lasting behavioral changes. This acquisition occurs through interaction with the environment and requires practice or experience. For instance, mastering a skill such as surfing requires considerable practice and experience, highlighting the essential role of repeated interactions with the environment in learning.
In contrast to learned behaviors, unlearned behaviors such as crying, sexual...
In contrast to learned behaviors, unlearned behaviors such as crying, sexual...
1.6K
01:14Avoidance Learning and Learned Helplessness
4.2K
Avoidance learning and learned helplessness are critical concepts in understanding behavioral responses to negative stimuli.
Avoidance learning occurs when an organism learns that a specific behavior can prevent an unpleasant outcome. For example, a student who receives a bad grade may start studying harder to avoid future poor grades. This behavior persists even when the negative outcome is no longer present. Avoidance learning is powerful because it maintains behavior in the absence of the...
Avoidance learning occurs when an organism learns that a specific behavior can prevent an unpleasant outcome. For example, a student who receives a bad grade may start studying harder to avoid future poor grades. This behavior persists even when the negative outcome is no longer present. Avoidance learning is powerful because it maintains behavior in the absence of the...
4.2K
01:21Cognitive Learning
1.6K
Cognitive learning is based on purposive behavior, incidental learning, and insight learning.
E. C. Tolman's theory of purposive behavior emphasizes that much behavior is goal-directed. He argued that to understand behavior, we must look at the entire sequence of actions leading to a goal. For instance, high school students study hard, not just due to past reinforcement but also to achieve the goal of getting into a good college.
Tolman introduced the idea that behavior is influenced by...
E. C. Tolman's theory of purposive behavior emphasizes that much behavior is goal-directed. He argued that to understand behavior, we must look at the entire sequence of actions leading to a goal. For instance, high school students study hard, not just due to past reinforcement but also to achieve the goal of getting into a good college.
Tolman introduced the idea that behavior is influenced by...
1.6K
01:22Purposive Learning
693
E. C. Tolman emphasized the purposiveness of behavior — the idea that much of our behavior is goal-directed. For instance, employees who aim for a promotion work diligently to meet their targets. Tolman argued that when classical conditioning and operant conditioning occur, the organism acquires certain expectations. In classical conditioning, a child might fear a dog because they expect it to bite. In operant conditioning, a person might consistently work overtime because they expect a...
693
01:12Observational Learning
1.5K
Albert Bandura's observational learning, also known as imitation or modeling, occurs when a person observes and imitates another's behavior. It is a quicker process than operant conditioning. A well-known example is the Bobo doll study, where children who saw an adult acting aggressively towards the doll were more likely to act aggressively when left alone, compared to those who observed a nonaggressive adult. Many psychologists view observational learning as a form of latent learning...
1.5K