的设计是为了控制蛋白质-蛋白质相互作用
Suzanne P van Wier1, Andrew M Beekman1
1School of Chemistry, Pharmacy & Pharmacology, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK. a.beekman@uea.ac.uk.
Chemical Society reviews
|January 16, 2025
概括
本综述详细介绍了针对蛋白质-蛋白质相互作用的质设计,这对于控制生物过程至关重要. 它涵盖了序列选择,优化和修改,以增强药物类似性质的药物应用.
科学领域:
- 药用化学 医学化学
- 结构生物学 结构生物学
- 计算生物学 计算生物学
背景情况:
- 准蛋白与蛋白相互作用 (PPI) 在生物科学中对于控制细胞过程至关重要.
- 低温电子显微镜 (cryo-EM) 和蛋白质结构预测工具 (例如AlphaFold,RosettaFold) 的进步加快了对PPI调制的兴趣.
- 体设计是开发抑制或稳定蛋白相互作用的分子的基本策略.
研究的目的:
- 提供关于调节蛋白质-蛋白质相互作用的化物设计过程的教程回顾.
- 突出选择初始序列的方法,有或没有结构数据.
- 讨论优化相关性和类似药物的特性的策略.
主要方法:
- 根据可用的结构信息或de novo设计选择初始序列.
- 在序列内分析关键残留物以指导优化.
- 提高的联结效率,亲和力和细胞透性的策略.
主要成果:
- 展示了针对PPI向的化物设计的系统方法.
- 识别方法来提高的有效性和药物相似性.
- 关于利用结构和序列信息来合理优化的指导.
结论:
- 体设计是开发针对蛋白质-蛋白质相互作用的治疗方法的强大起点.
- 优化序列,配体效率和物理化学性质是成功发现基于的药物的关键.
- 进一步的修改可以增强的亲和力和细胞透性,提高它们作为药品的潜力.
更多相关视频
11:09Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation
Published on: August 1, 2018
10.7K
06:50Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
Published on: January 26, 2024
1.6K
相关概念视频
Protein-protein Interfaces
12.4K
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...
12.4K
Protein Networks
3.9K
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,...
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,...
3.9K
Protein Folding
7.7K
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
7.7K
Protein Organization
6.2K
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....
The primary structure of a protein is its amino acid sequence....
6.2K
Protein-Protein Interfaces
3.6K
3.6K
Ligand Binding Sites
12.7K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
12.7K
