Influence of non-protein amino-acid mimosine in peptide conformational propensities from novel Amber force field parameters

Mimosine is a non-protein amino acid derived from plants known for its ability to bind to divalent or trivalent metal cations such as Zn$^{2+}$, Ni$^{2+}$, Fe$^{2+}$ or Al$^{3+}$. This results in interesting antimicrobial and anti-cancer properties, which make mimosine a promising candidate for therapeutic applications. One possibility is to incorporate mimosine into synthetic short peptide drugs. However, our understanding of how this amino acid affects peptide structure is still limited, reducing our ability to design effective therapeutic compounds. In this work, we used computer simulations to understand this question. We first build parameters for the mimosine residue to be used in combination with two classical force fields of the Amber family. Then, we used atomistic molecular dynamics simulations with the resulting parameter sets to evaluate the influence of mimosine in the structural propensities for this amino acid. We compared the results of these simulations with identical peptides where mimosine is replaced by either phenylalanine or tyrosine. We found that the strong dipole in mimosine induces a preference for conformations where the amino acid rings are stacked over more traditional conformations. We validated our results using quantum mechanical calculations, which provide a robust foundation to the outcome of our classical simulations.