SERS, docking and MD simulations of 2-methylene-4-oxo-4-[(3,4,5-trichlorophenyl)amino]butanoic acid (MTB): experimental and DFT modeling

Abstract

The search for effective molecular probes and drug candidates requires a clear understanding of their structural, spectroscopic, and biological behavior. In this work, we investigated 2-methylene-4-oxo-4-[(3,4,5-trichlorophenyl)amino]butanoic acid (MTB) through a combination of experimental and computational approaches. Surface-enhanced Raman scattering (SERS) was measured at different concentrations, while theoretical SERS simulations were performed with Ag₆ clusters positioned at the most reactive sites of the molecule. Density functional theory (DFT) calculations, molecular docking, and molecular dynamics (MD) simulations were further employed to explore the electronic properties and binding interactions of MTB with the 4Z8D protein, both in its free form and when complexed with silver clusters. The results show that MTB binds strongly to Ag atoms through chemisorptions and adopts a tilted orientation that changes with concentration. Among the protein-ligand systems, the 4Z8D-MTB-Ag₆-W1 complex was the most stable, stabilized by a combination of lipophilic, electrostatic, and hydrogen-bonding interactions. These findings highlight MTB as a promising bioactive-candidate whose performance is enhanced in the presence of silver clusters, offering useful insights for drug design and therapeutic development.