Influence of the Nonprotein Amino Acid Mimosine in Peptide Conformational Propensities from Novel Amber Force Field Parameters

[Image: see text] Mimosine is a nonprotein amino acid derived from plants known for its ability to bind to divalent and trivalent metal cations such as Zn(2+), Ni(2+), Fe(2+), or Al(3+). This results in interesting antimicrobial and anticancer properties, which make mimosine a promising candidate for therapeutic applications. One possibility is to incorporate mimosine into synthetic short peptide drugs. However, how this amino acid affects the peptide structure is not well understood, reducing our ability to design effective therapeutic compounds. In this work, we used computer simulations to understand this question. We first built 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 homologous 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 extended conformations. We validated our results using quantum mechanical calculations, which provide a robust foundation for the outcome of our classical simulations.