%0 Journal Article %A Alice Coucke %A Guido Uguzzoni %A Francesco Oteri %A Simona Cocco %A Remi Monasson %A Martin Weigt %T Direct coevolutionary couplings reflect biophysical residue interactions in proteins %D 2016 %R 10.1101/061390 %J bioRxiv %P 061390 %X Coevolution of residues in contact imposes strong statistical constraints on the sequence variability between homologous proteins. Direct-Coupling Analysis (DCA), a global statistical inference method, successfully models this variability across homologous protein families to infer structural information about proteins. For each residue pair, DCA infers 21×21 matrices describing the coevolutionary coupling for each pair of amino acids (or gaps). To achieve the residue-residue contact prediction, these matrices are mapped onto simple scalar parameters; the full information they contain gets lost. Here, we perform a detailed spectral analysis of the coupling matrices resulting from 70 protein families, to show that they contain quantitative information about the physico-chemical properties of amino-acid interactions. Results for protein families are corroborated by the analysis of synthetic data from lattice-protein models, which emphasizes the critical effect of sampling quality and regularization on the biochemical features of the statistical coupling matrices. %U https://www.biorxiv.org/content/biorxiv/early/2016/06/29/061390.full.pdf