生成性景观和动力学设计多域人工跨膜传送器
bioRxiv : the preprint server for biology
|April 16, 2025
概括
我们开发了一种新的蛋白质设计方法,将潜伏生成景观 (LGL) 和分子动力学 (MD) 结合起来,以创建功能性蛋白质. 这种方法成功地设计了具有类似本土功能的新型铜运输器.
科学领域:
- 计算生物学是一种计算生物学.
- 蛋白质工程是一种蛋白质工程.
- 生物物理学的生物物理.
背景情况:
- 设计具有特定功能的蛋白质是复杂的,因为相互关联的因素,如折叠,动态和功能.
- 蛋白序列中的进化约束保持了可以预测新型功能序列的模式.
研究的目的:
- 为新的蛋白质设计开发和验证一个集成的计算和实验工作流.
- 探索未知的蛋白质序列空间并创建新的功能蛋白质.
主要方法:
- 利用潜伏生成景观 (LGL) 框架来学习进化模式和预测功能序列.
- 采用分子动力学 (MD) 模拟来分析设计蛋白质的结构动力学关系.
- 结合LGL和MD与生物化学表征,用于全面的设计和验证过程.
主要成果:
- 成功设计和表征了两个人工多域ATP驱动的跨膜铜输送器.
- 设计的运输器表现出与本地类似的功能.
- 综合工作流有效地揭示了蛋白质序列,结构和功能之间的复杂关系.
结论:
- 结合LGL,MD和生物化学表征的协同工作流是探索序列空间和设计功能蛋白质的有效方法.
- 这种综合性方法可以更深入地了解控制蛋白质结构和动态的相互依存关系.
- 该方法对推进新型蛋白质设计和工程复杂生物系统具有前景.
相关概念视频
The Significance of Membrane Transport
20.3K
The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
20.3K
Insertion of Multi-pass Transmembrane Proteins in the RER
7.6K
The rough ER membrane synthesizes, assembles, and embeds transmembrane proteins in diverse topologies. These proteins function as transporters or channels and can remain in the ER membrane or are sent to the Golgi complex, lysosome, and cell membrane.
The multipass transmembrane proteins are the type IV integral membrane proteins with multiple topogenic sequences determining their spatial arrangement in the ER membrane. Nearly all multipass proteins lack a cleavable signal sequence and use...
The multipass transmembrane proteins are the type IV integral membrane proteins with multiple topogenic sequences determining their spatial arrangement in the ER membrane. Nearly all multipass proteins lack a cleavable signal sequence and use...
7.6K
Primary Active Transport
172.8K
In contrast to passive transport, active transport involves a substance being moved through membranes in a direction against its concentration or electrochemical gradient. There are two types of active transport: primary active transport and secondary active transport. Primary active transport utilizes chemical energy from ATP to drive protein pumps that are embedded in the cell membrane. With energy from ATP, the pumps transport ions against their electrochemical gradients—a direction...
172.8K
Carrier-Mediated Transport
217
Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
217
Cellular Membranes and Drug Transport
238
Drugs must traverse multiple biological barriers, such as multi-layered skin, single-layered intestinal epithelium, and the plasma membrane, to reach their target sites within the body. The plasma membrane, a highly structured composite of phospholipids, carbohydrates, and proteins, is the cell's protective boundary, facilitating selective substance exchange.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
238
Multi-pass Transmembrane Proteins and β-barrels
5.2K
In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as...
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as...
5.2K


