title: The molecular mechanism of the ligand exchange reaction of an antibody against a glutathione-coated gold cluster.
abstract: The labeling of proteins with heavy atom clusters is of paramount importance in biomedical research, but its detailed molecular mechanism remains unknown. Here we uncover it for the particular case of the anti-influenza N9 neuraminidase NC10 antibody against a glutathione-coated gold cluster by means of ab initio QM/MM calculations. We show that the labeling reaction follows an associative double SN2-like reaction mechanism, involving a proton transfer, with low activation barriers only if one of the two distinct peptide/peptidic ligands (the one that occupies the side position) is substituted. Positively charged residues in the vicinity of the incoming thiol result in strong interactions between the antibody and the AuMPC, favoring the ligand exchange reaction for suitable protein mutants. These results pave the way for future investigations aimed at engineering biomolecules to increase their reactivity towards a desired gold atom cluster.
authors.affiliation: Departament de Química Inorgànica i Orgànica (Secció Química Orgànica) & Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain. c.rovira@ub.edu.
authors.forename: Víctor
authors.initials: V
authors.lastname: Rojas-Cervellera
authors.affiliation: Departament de Química Inorgànica i Orgànica (Secció Química Orgànica) & Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain. c.rovira@ub.edu.
authors.forename: Lluís
authors.initials: L
authors.lastname: Raich
authors.affiliation: Department of Physics, Tampere University of Technology, P.O. Box 692, FI-33101 Tampere, Finland and COMP Centre of Excellence, Department of Applied Physics, Aalto University, FI-00076 Aalto, Finland and Department of Physics. Norwegian University of Science and Technology, NO-7491 Trondheim, Norway.
authors.forename: Jaakko
authors.identifier: http://orcid.org/0000-0001-9037-7095
authors.initials: J
authors.lastname: Akola
authors.affiliation: Departament de Química Inorgànica i Orgànica (Secció Química Orgànica) & Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain. c.rovira@ub.edu and Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys, 23, 08020 Barcelona, Spain.
authors.forename: Carme
authors.identifier: http://orcid.org/0000-0003-1477-5010
authors.initials: C
authors.lastname: Rovira