Binding Metal Ions to Peptides

1. Binding Metal Ions to Peptides Robert C. Dunbar1, Nick C. Polfer2, Giel Berden3, Jos Oomens3,4 1Case Western Reserve University 2University of Florida 3FOM Institute for Plasma Physics, (Netherlands) 4University of Amsterdam Introduction A computational survey comparing the propensities for charge-solvation (CS) versus amide-nitrogen (Iminol) binding of metal ions to simple peptide chains. Iminol (Amide-N) Dipeptide Charge-Solvated (CS) Dipeptide Iminol Tripeptide CS Tripeptide Results Purpose Survey thermodynamically preferred binding mode of attachment to simple peptides for interesting metal ions in normal oxidation states. Methods Computations were DFT/B3LYP. Basis 6-31+g(d,p). All-electron calculations up to Ga3+, sdd effective core potential for metals heavier than Ga3+. Key: Full color = Preference > 50 kJ/mol Medium color = Preference 20 – 50 kJ/mol Weak color = Preference < 50kJ/mol Note: Ba2+AlaAla, Sr2+AlaAla and Ca2+AlaAla spectra indicate full or partial conversion to CS/Zwitterion conformation Conclusions • Iminol binding is favored vs CS for • Metals with valence d electrons • Higher metal charge • Smaller metal ions • CS binding universalfor+1 metal ions • For +2 and+3 ions, governed byd electrons and size • Not much difference between dipeptide and tripeptide • Same deprotonated amide-N preferences as in solution: • Pd+2 (153 kJ/mol) > Cu+2 (98) > Ni+2 (53) ≥ Co+2 (51) Background • In condensed phases, metal ions like Na+, K+. Ca2+ normally bind peptides at exposed Lewis-basic sites. But active metal ions can deprotonate the amide linkages and bind the amide nitrogens. Propensities are in the order • Pd2+ > Cu2+ > Ni2+ > Co2+ • (I. Sovago, quoted by B. Martin, ”Peptide Bond Characteristics” in “Metal Ions in Biological Systems,” • Sigel and Sigel, Eds., Marcel Dekker, 1988, Vol 38.) • We recently observed the corresponding binding mode in some gas-phase complexes of Mg2+, Ni2+ and Co2+. This is the iminol binding mode, distinguished from charge-solvation (CS) binding in the IRMPD spectrum by the absence of the Amide II vibration (~1500-1550 cm-1) of the peptide. • There is little experimental information about these binding modes for simple polyalanines because the complexes are difficult to prepare. Illustrated here are literature IRMPD spectra for the tripeptide FGG (Dunbar, Polfer, Berden, Oomens, IJMS 330-332, 71 (2012)). The present study is a computational survey of the expected binding propensities for the fundamentally interesting polyalanine ligands. Acknowledgments This work is financially supported by the “Nederlandse Organisatie voor Wetenschappelijk Onderzoek” (NWO). We thank SARA Computing and Networking Services (www.sara.nl) for their support in using the Lisa Compute Cluster.

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