Thesis Title

Investigation of the Effect of Neurotransmitters on Brain-Derived Neurotrophic Factor (BDNF) Protein Using Molecular Dynamics

Abstract

This dissertation uses molecular dynamics simulations to examine the interactions of acetylcholine, dopamine, GABA, glutamate, and serotonin with BDNF and β-amyloid. Under external electric fields, each neurotransmitter adopted distinct active conformations (ACh, dopamine, serotonin, and glutamate under low-intensity fields, and GABA under higher fields). Serotonin and dopamine stabilized BDNF’s structure, whereas GABA induced destabilization, with the BDNF A-chain showing the highest binding affinity.
Dopamine and L-DOPA substantially reduced β-amyloid stability and toxicity, outperforming catechol. Their stronger effects were linked to combined hydrophobic and hydrogen-bond interactions, while catechol interacted mainly through hydrophobic contacts. Electronic analyses showed that catechol’s weaker inhibition stems from greater electron localization and anti-aromaticity. Overall, the findings highlight dopamine and L-DOPA as promising candidates for developing Alzheimer’s therapeutic strategies.