Structural Insight on Interaction of NMDA receptor with fentanyl, ketamine and Isoflurane: A Computational Study to Unravel Mode of Binding.

NMDA receptors are targets for anesthetics like isoflurane, ketamine, and fentanyl, which inhibit channel activation at clinically relevant concentrations. The binding modes of these drugs are poorly understood. Using molecular docking, molecular dynamics simulations, and DFT calculations, the study found that ketamine, isoflurane, and fentanyl have high docking scores and significant interactions with the NMDA receptor, binding to the substrate-binding pocket with stable interactions and low HOMO-LUMO energy gaps. The results provide evidence of strong and stable binding between these drugs and the NMDA receptor.

Study at a glance

Abstract

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.