Simulated point mutations in the Aalpha-chain of human fibrinogen support a role of the alphaC domain in the stabilization of fibrin gel.

The hydrophobicity pattern distribution in the Aalpha-, Bbeta- and gamma-chains of human fibrinogen has been studied by a nonlinear method, recurrence quantification analysis, in the wild type and in a number of naturally occurring or simulated mutants. The aim was to find a structural basis for distinguishing between silent and pathological mutants. We were successful in the case of mutations on the Aalpha-chain, thanks to the peculiar features of this chain as compared to the other two. Relevant findings concerning the point mutants of the Aalpha-chain are the following: (a) the recurrence quantification analysis-based classification of such mutants is in good agreement with the clinical classification, and (b) the location of the mutated residue on the sequence plays a more relevant role than its hydrophobic features. Artificial point mutants in the terminal zone (600-866 residues) of the extended isoform of the Aalpha-chain cluster together with the natural hemorrhagic mutants of the first (1-207) residues.