<b>Docking and MD simulation initial structures</b>

Our research centered on the NLRP3 protein, which plays a pivotal role in the context of neuroinflammation, a major contributing factor in Alzheimer's Disease (AD). When NLRP3 is activated, it releases inflammatory molecules that worsen brain damage. Our aim was to identify potential compounds that can inhibit NLRP3 and reduce inflammation in neurons, possibly providing a way to treat AD. A computational approach was utilized to screen a library of coumarin derivatives for compounds that meet drug-like criteria and could potentially penetrate the blood-brain barrier. We identified three promising coumarin-based compounds with better NLRP3-binding affinity than a known inhibitor. Our molecular dynamics simulations and binding energy calculations further supported these compounds as potential leads for inhibiting the NLRP3 inflammasome and potentially treating AD.