Khalid Atif, Farhat Nabeela
Department of Anaesthesiology, Veeranga AvantiBai Lodhi Autonomous State Medical College, Etah, India.
School of Energy Science and Engineering, IIT Guwahati, Guwahati, India.
Cell Biochem Biophys. 2025 Mar;83(1):669-677. doi: 10.1007/s12013-024-01499-z. Epub 2024 Sep 4.
NMDA receptors are considered targets for many anesthetics if they are modulated by the drugs at clinically relevant concentrations. Volatile anesthetics like isoflurane and ketamine interact with NMDA receptors, inhibiting channel activation and thus blocking NMDA neurotransmission at clinically relevant concentrations. The mode of binding of commonly used drugs like ketamine, isoflurane, and fentanyl is poorly understood. We used molecular docking, molecular dynamics simulations, and DFT calculation of these drugs against the NMDA receptor. Using well-defined computational methods, we identified that these drugs have high docking scores and significant interaction with receptors. These drugs bind to the substrate-binding pocket and form a remarkable number of interactions. We have found that these interactions are stable and have low HOMO-LUMO energy gaps. This study provides enough evidences of strong and stable interaction between drugs and NMDA receptor.
如果N-甲基-D-天冬氨酸（NMDA）受体在临床相关浓度下受到药物调节，那么它们就被认为是许多麻醉剂的作用靶点。异氟烷和氯胺酮等挥发性麻醉剂与NMDA受体相互作用，在临床相关浓度下抑制通道激活，从而阻断NMDA神经传递。氯胺酮、异氟烷和芬太尼等常用药物的结合模式尚不清楚。我们对这些药物与NMDA受体进行了分子对接、分子动力学模拟和密度泛函理论（DFT）计算。通过使用明确的计算方法，我们确定这些药物具有高对接分数且与受体有显著相互作用。这些药物与底物结合口袋结合并形成大量相互作用。我们发现这些相互作用是稳定的，且最高占据分子轨道（HOMO）-最低未占分子轨道（LUMO）能隙较低。本研究提供了足够的证据证明药物与NMDA受体之间存在强烈且稳定的相互作用。
