针对T型通道的FDA批准的药物的In Silico识别和建模
Pedro Fong1,2, Susana Roman Garcia3, Melanie I Stefan4
1Faculty of Health Sciences and Sports, Macao Polytechnic University, Macao SAR, China.
PloS one
|August 8, 2025
概括
研究人员确定了蒙特卢卡斯特作为一种潜在的药物,通过计算阻止Cav3.1 T型通道来治疗神经疾病. 这种FDA批准的药物显示出高的结合亲和力和稳定性,可能会减少突触囊泡的释放.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 计算生物学 计算生物学
背景情况:
- 抑制Cav3.1 T型通道显示出治疗和糖尿病神经病变等神经系统疾病的前景.
- 识别现有的FDA批准的药物用于重新使用可以加速治疗的发展.
研究的目的:
- 通过计算选FDA批准的药物,以检测它们与Cav3.1 T型通道的潜在结合.
- 通过in silico方法确定用于神经疾病治疗的候选药物.
主要方法:
- 使用GOLD v5.5对2,115种FDA批准的药物进行分子对接,以对抗Cav3.1通道.
- 雇佣的ChemPLP评分用于约束亲和度估计.
- 进行了MMPBSA,MMGBSA,MD和MCell模拟,以验证结合和评估功能影响.
主要成果:
- 在对接模拟中,蒙特卢卡斯特对Cav3.1通道表现出高的结合亲和力.
- 进一步的模拟证实了蒙特卢卡斯特-Cav3.1复合物的稳定性.
- MCell模拟表明,蒙特卢卡斯特减少了突触囊泡的释放,影响了神经元的信号传递.
结论:
- 蒙特卢卡斯特是一种有前途的候选药物,可用于治疗涉及Cav3.1.1.的神经疾病.
- 药物的特性表明它可以穿越血脑屏障并调节Cav3.1功能.
- 计算查提供了一种有效的方法来识别新型治疗剂.
更多相关视频
07:26Cell-based Calcium Assay for Medium to High Throughput Screening of TRP Channel Functions using FlexStation 3
Published on: August 17, 2011
21.3K
05:08Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins
Published on: July 8, 2025
357
相关概念视频
01:18Antihypertensive Drugs: Action of Calcium Channel Blockers
770
Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...
770
01:26Targets for Drug Action: Overview
7.4K
Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
7.4K
01:20Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers
990
Class IV antiarrhythmic drugs, such as verapamil and diltiazem, block calcium channels. They primarily affect the heart, slowing the conduction in calcium-dependent tissues like the SA and AV nodes. These drugs manage reentrant supraventricular tachycardia (SVT) and reduce ventricular rate in atrial flutter/fibrillation.
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
990
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.6K
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...
2.6K
01:17Antiepileptic Drugs: Calcium Channel Blockers
624
Calcium channel blockers, a class of antiepileptic drugs, regulate the flow of calcium ions within neurons.
Calcium channel blockers exert their antiepileptic effects by targeting T-type calcium channels, which are integral to transmitting nerve signals in the central nervous system. These channels allow the passage of calcium ions, which are vital for neuronal communication. By inhibiting T-type calcium channels, calcium channel blockers effectively reduce the release of neurotransmitters and...
Calcium channel blockers exert their antiepileptic effects by targeting T-type calcium channels, which are integral to transmitting nerve signals in the central nervous system. These channels allow the passage of calcium ions, which are vital for neuronal communication. By inhibiting T-type calcium channels, calcium channel blockers effectively reduce the release of neurotransmitters and...
624
01:15G Protein-coupled Receptors
13.4K
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
13.4K