Abstract
There is a growing interest amongst researchers across the globe to study drug-protein interactions since the pharmacokinetics of drug depends upon their binding with the protein. Human serum albumin (HSA) is a liver synthesized protein found in blood plasma and associated with the transport of many substances, including hormones and drugs. Memantine is an oral NMDA glutamate receptor antagonist used to treat Alzheimer's disease (AD) and dementia. This study intends to delineate the interaction of memantine with HSA employing various biophysical and computational approaches. First, molecular docking was performed between Memantine and HSA to see their affinity and possible interactions. Then, the docking results were further validated by molecular dynamics (MD) simulations and essential dynamics. The MD simulation results showed that the docked complex of Memantine-HSA was stable in the MD trajectory. Fluorescence-based binding studies revealed that memantine shows a good binding affinity to HSA with a binding constant (K) of 10(6) M-1. Moreover, Isothermal titration calorimetry (ITC) advocated the impulsive binding between memantine and HSA, validating the in-silico observations. Overall, the study suggested that Memantine can be a potential binding partner of HSA and can be optimized further in AD therapy after required validation. (C) 2021 Elsevier B.V. All rights reserved.