Accuracy of Density Functionals in the Prediction of Electronic Proton Affinities of Amino Acid Side Chains.

Abstract

The ionization states of amino acids influence the structure, function, stability, solubility, and reactivity of proteins and are difficult to determine unambiguously by experimental means. Thus, it is very important to be able to determine them theoretically and with high reliability. We have analyzed how well DFT functionals, often used to characterize complex and large models such as proteins, describe the zero-point-exclusive proton affinity at 0 K, PAel0K, for the ionizable side chains of lysine (Lys), histidine (His), arginine (Arg), and aspartate (Asp–) as well as the cysteine (Cys–), serine (Ser–), and tyrosine (Tyr–) anions. The reference values PAel0K were determined at the very accurate CCSD(T)/CBS level. Those values were obtained by the sum of the complete basis set limit of the MP2 energies plus a CCSD(T) correction term evaluated with the aug-cc-pVTZ basis set. The complete basis set limit of MP2 energies was determined using the Truhlar and Helgaker extrapolation schemes. A new, important,...