Effects of Substituted Tryptamines on the Excitonic Structure of the Tubulin Tryptophan Network

Microtubules contain ordered aromatic amino acid networks whose optical excitations have been proposed to support non-trivial energy-transfer dynamics. Here, we examined whether bound tryptamine ligands can perturb the excitonic structure of the tubulin tryptophan network. A virtual screen of 294 tryptamines was performed across seven known binding regions of the tubulin heterodimer using AutoDock Vina 1.2.6. From this screen, top-ranked tryptamine ligands were carried forward for excited-state analysis. Geometry optimization and time-dependent density functional theory (TD-DFT) calculations were used to obtain vertical excitation energies and transition dipole moments for the ligand-bound states in the ultraviolet range. These ligand properties were then incorporated into a tight-binding Hamiltonian describing the tubulin tryptophan excitation network in order to evaluate changes in exciton energies and eigenvector delocalization. The calculations indicate that tryptamine binding can modify the excitonic landscape of tubulin in a ligand-dependent manner, with the magnitude of the perturbation governed by excitation wavelength, transition dipole strength, and spatial orientation relative to the intrinsic tryptophan network. These results show that substituted tryptamines differ in how they perturb the modeled tubulin tryptophan excitonic manifold, but they do not by themselves establish experimentally resolvable modulation of tubulin or microtubule photophysics. The present work should therefore be interpreted as a first-pass computational screening framework for prioritizing ligands and defining future experimental tests.