Thorough theoretical search of conformations of neutral, protonated and deprotonated glutamine in gas phase

Conformations and Metal Ion Affinities of Glutamine Binding with Alkali and Alkaline Earth Metal Cations: an ab initio Study

“…For Gln•K + , Gln•Rb + , and Gln•Cs + , however, the global energy minima are zwitterions as predicted by B3LYP, but are canonical conformers as predicted by BHandHLYP and MP2. Based on B3LYP results, it has been concluded that the size of metal ion is the dominant factor for the global minimum to take the zwitterionic form [26]. The present BHandHLYP and MP2 results indicate that the conclusion may be only a B3LYP biased claim.…”

“…In principle, the full conformational space of a biomolecule may be thoroughly searched by optimizing trial structures generated by combinations of varying all rotational degrees of freedom. The thorough conformational search method has been successfully applied to many small biomolecules, including Gln [26]. Systematic searches of the structures of protonated, hydrated and metalated amino acid complexes have also been performed [4,5,21,22].…”

“…Since the free energy change is probed more directly than the enthalpy change in experiments and the effective experimental temperature is often close to 500 K, deducing the enthalpy change at T =298 K from the experiment may sometime cause significant error. In fact, it has been shown that the SKM result underestimates the protonation energy of Gln by about 30 kJ/mol [26,41]. Due to the similarity in the metalation and protonation processes, some underestimation of SKM on MIA is expected.…”

“…The conformations of Gln reported in Ref. [26] are used here. To our knowledge, only the MIAs of Gln with Na + and K + have been published [7,9,10,13].…”

“…Furthermore, the existing theoretical results are often obtained by conformational search based on Monte Carlo sampling using molecular mechanics force fields that are prone to missing important conformers [25]. To improve the reliability of the computational results, extensive systematic conformational searches of the potential energy surfaces are required [26].…”