Sampling the protonation states: pH-dependent UV absorption spectrum of a polypeptide dyad

When a chromophore interacts with titrable molecular sites, the modeling of its photophysical properties requires to take into account all their possible protonation states. We have developed a multi-scale protocol, based on constant-pH molecular dynamics simulations coupled to QM/MM excitation energy calculations, aimed at sampling both the phase space and protonation state space of a short polypeptide featuring a tyrosine–tryptophan dyad interacting with two aspartic acid residues. We show that such a protocol is accurate enough to reproduce the tyrosine UV absorption spectrum at both acidic and basic pH. Moreover, it is confirmed that UV-induced radical tryptophan is reduced thanks to an electron transfer from tyrosine, ultimately explaining the complex pH-dependent behavior of the peptide spectrum.