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Abstract

We studied acetylhistidine (AcH), bare or microsolvated with a zinc cation by
simulations in isolation. First, a global search for minima of the potential
energy surface combining both, empirical and first-principles methods, is
performed individually for either one of five possible protonation states.
Comparing the most stable structures between tautomeric forms of negatively
charged AcH shows a clear preference for conformers with the neutral imidazole
ring protonated at the N-epsilon-2 atom. When adding a zinc cation to the
system, the situation is reversed and N-delta-1-protonated structures are
energetically more favorable. Obtained minima structures then served as basis
for a benchmark study to examine the goodness of commonly applied levels of
theory, i.e. force fields, semi-empirical methods, density-functional
approximations (DFA), and wavefunction-based methods with respect to high-level
coupled-cluster calculations, i.e. the DLPNO-CCSD(T) method. All tested force
fields and semi-empirical methods show a poor performance in reproducing the
energy hierarchies of conformers, in particular of systems involving the zinc
cation. Meta-GGA, hybrid, double hybrid DFAs, and the MP2 method are able to
describe the energetics of the reference method within chemical accuracy, i.e.
with a mean absolute error of less than 1kcal/mol. Best performance is found
for the double hybrid DFA B3LYP+XYG3 with a mean absolute error of 0.7 kcal/mol
and a maximum error of 1.8 kcal/mol. While MP2 performs similarly as
B3LYP+XYG3, computational costs, i.e. timings, are increased by a factor of 4
in comparison due to the large basis sets required for accurate results.