A comparative structural genomic analysis of a new class of metal-trafficking proteins can provide insights into the intracellular chemistry of reactive cofactors such as copper and zinc. Starting from the sequences of the metallochaperone Atx1 and from the first soluble domain of the copper-transporting ATPase Ccc2, both from yeast, a search on the available genomes was performed using a homology criterion and a metal-binding motif x‘-x"-C-x‴-x⁗-C. By limiting ourselves to 20% identity with any of the proteins found, several soluble copper-transport proteins were identified, as well as soluble domains of membrane-bound ATPases. Structural models were calculated using high-resolution solution structures as templates, and the models were validated using statistical and energy criteria. Residue conservation and substitution have been interpreted and discussed in terms of structure–function relationship. The potential energy surfaces have been analyzed in terms of protein–protein interactions. We find that metallochaperones and their physiological partner ATPases from several phylogenetic kingdoms recognize one another, via an interplay of electrostatics, hydrogen bonding, and hydrophobic interactions, in a manner that precisely orients the metal-binding side chains for rapid metal transfer between otherwise tight binding sites. Finally, other putative metal-transport proteins are mentioned that have low homology and/or a different metal-binding consensus motif and that appear to use similar structures for recognition and transfer. This analysis highlights the wealth and the complexity of the field.

The interaction between Cu(II) and the rat amyloid β (1–28) fragment in micellar solutions at pH 7.5 was investigated by CD and NMR spectroscopy; the proton–copper distances were used in restrained molecular dynamics simulations to obtain a structural model of the Cu(II) complex.

Using density functional theory (DFT) and its time-dependent (TD) extension, the electronic and optical properties of the hexathiapentacene (HTP) molecule, a derivative of pentacene (PNT) obtained by symmetric substitution of the six central H atoms with S atoms, are investigated for its gas and solid phases. For the molecular structure, all-electron calculations are performed using a Gaussian localized orbital basis set in conjunction with the Becke three-parameter Lee-Yang-Parr (B3LYP) hybrid exchange-correlation functional. Electron affinities, ionization energies, quasiparticle energy gaps, optical absorption spectra, and exciton binding energies are calculated and compared with the corresponding results for PNT, as well as with the available experimental data. The DFT and TDDFT results are also validated by performing many-body perturbation theory calculations within the $GW$ and Bethe-Salpeter equation formalisms. The functionalization with S atoms induces an increase of both ionization energies and electron affinities, a sizable reduction of the fundamental electronic gap, and a redshift of the optical absorption onset. Notably, the intensity of the first absorption peak of HTP falling in the visible region is found to be nearly tripled with respect to the pure PNT molecule. For the crystal structures, pseudopotential calculations are adopted using a plane-wave basis set together with the Perdew-Burke-Ernzerhof exchange-correlation functional empirically corrected in order to take dispersive interactions into account. The electronic excitations are also obtained within a perturbative B3LYP scheme. A comparative analysis is carried out between the ground-state and excited-state properties of crystalline HTP and PNT linking to the findings obtained for the isolated molecules.