利用深度学习方法用于电压门离子通道药物发现
Diego Lopez-Mateos1,2, Brandon John Harris1,2, Adriana Hernández-González1,2
1Department of Physiology and Membrane Biology, University of California School of Medicine, Davis, California, United States.
Physiology (Bethesda, Md.)
|August 27, 2024
概括
深度学习,特别是扩散模型,现在可以通过计算来设计电压离子通道 (VGIC) 的蛋白质结合剂. 这种方法为开发选择性VGIC药物来治疗疼痛和心律失常等疾病提供了新的策略.
科学领域:
- 生物化学 生物化学
- 计算生物学 计算生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 电压离子通道 (VGIC) 对于细胞电活动至关重要,也是主要的药物点.
- 为VGICs开发选择性药物仍然是制药研究中的一个重大挑战.
研究的目的:
- 审查用于计算蛋白质设计的深度学习和扩散模型的进展.
- 探索这些方法在设计VGIC的结合剂中的应用.
- 为开发针对VGIC的新型治疗提供框架.
主要方法:
- 利用深度学习和扩散模型用于计算蛋白质绑定器设计.
- 在设计工作中利用VGIC的最新结构数据.
- 分析各种VGIC区域 (孔隙,电压传感域,辅助子单位接口) 的设计策略.
主要成果:
- 深度学习使蛋白质结合剂的基于结构的计算设计成为可能.
- 越来越多的VGIC实验结构数据支持计算设计.
- 设计针对特定VGIC域的绑定器的潜力.
结论:
- 使用扩散模型的计算蛋白质设计显示了VGIC药物发现的前景.
- 这些方法可以解决VGIC药理学中的选择性挑战.
- 为VGIC相关疾病提供了新,有效和安全的治疗方法.
相关概念视频
Voltage-gated Ion Channels
8.1K
Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several...
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several...
8.1K
Patch Clamp
5.4K
Many fundamental cell functions such as muscle contraction and nerve transmission rely on the electrical signals produced by the movement of positively and negatively charged ions across the cell membrane. One competent method to record current flowing across the whole cell or single ion channel is the patch-clamp technique.
In this method, a glass micropipette containing electrolyte solution is tightly sealed against a small portion of the cell membrane. As a result, a patch of the cell...
In this method, a glass micropipette containing electrolyte solution is tightly sealed against a small portion of the cell membrane. As a result, a patch of the cell...
5.4K
Ligand-gated Ion Channels
12.3K
Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
12.3K
Non-gated Ion Channels
6.7K
Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism....
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism....
6.7K
Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.2K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.2K
The Role of Ion Channels in Neuronal Computation
3.2K
A postsynaptic neuron usually receives numerous impulses from several other presynaptic neurons. The axon hillock of the postsynaptic neuron integrates all these signals and determines the likelihood of firing an action potential.
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential....
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential....
3.2K


