Cooperativity in bimetallic glutathione complexes.
Glutathione interacting with Au(+), Ag(+), and [HgMe](+) metal ions is investigated using density functional theory. An extensive conformational search shows that the sulfhydryl group of cysteine is the predominant binding motif for Au(+), Ag(+), and [HgMe](+). The order of binding affinities and binding free energies for the metal:ligand complexes are calculated at the B3LYP-D3(BJ)/def2-TZVP level of theory. Analysis of the gas-phase optimized structures has shown that the increase in the number of metal ions (1:1 → 2:1) during the complex formation with a single glutathione leads to a strong cooperative behavior. Conversely, anti-cooperativity is demonstrated in implicit solvation corrections as well as in explicit solvent corrections to the energies in the explicitly solvated-phase structures optimized using a density-based adaptive QM/MM methodology.
Theoretical Chemistry, Organic Chemistry Institute, Westfälische Wilhelms Universität Münster, Correnstrasse 40, Münster, 48149, Germany.
Sadhana
S
Kumbhar
Department of Chemistry, Indian Institute of Technology Kharagpur, 721 302, India.
Saibal
S
Jana
Department of Chemistry, Indian Institute of Technology Kharagpur, 721 302, India. Electronic address: anoop@chem.iitkgp.ernet.in.
Anakuthil
A
Anoop
Theoretical Chemistry, Organic Chemistry Institute, Westfälische Wilhelms Universität Münster, Correnstrasse 40, Münster, 48149, Germany. Electronic address: m.waller@uni-muenster.de.
Mark P
MP
Waller
D001665:Binding Sites; D003198:Computer Simulation; D056831:Coordination Complexes / Q000737:chemistry*; D005978:Glutathione / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D006860:Hydrogen Bonding; D008628:Mercury / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D011789:Quantum Theory; D012834:Silver / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics
D056831:Coordination Complexes; D012997:Solvents; D012834:Silver; D006046:Gold; D008628:Mercury; D005978:Glutathione
Adaptive QM/MM; Bimetallic; Cooperativity; Double mutant cycle; Glutathione