Quantum Mechanics Approach to Hydration Energies and Structures of Alanine and Dialanine

Abstract

A systematic approach to the phenomena related to hydration of biomolecules is reported at the state of the art of electronic-structure methods. Large-scale CCSD(T), MP4-SDQ, MP2, and DFT(M06-2X) calculations for some hydrated complexes of alanine and dialanine (Ala⋅13 H O, Ala H ⋅18 H O, and Ala ⋅18 H O) are compared with experimental data and other elaborate modeling to assess the reliability of a simple bottom-up approach. The inclusion of a minimal number of water molecules for microhydration of the polar groups together with the polarizable continuum model is sufficient to reproduce the relative bulk thermodynamic functions of the considered biomolecules. These quantities depend on the adopted electronic-structure method, which should be chosen with great care. Nevertheless, the computationally feasible MP2 and M06-2X functionals with the aug-cc-pVTZ basis set satisfactorily reproduce values derived by high-level CCSD(T) and MP4-SDQ methods, and thus they are suitable for future developments of more elaborate and hence more biochemically significant peptides.

The water molecule arrangement over the side chain of some aliphatic amino acids: A quantum chemical and bottom‐up investigation

“…The shape of the Ala · 13H 2 O complex has been derived from the Gly · 13H 2 O complex, replacing the hydrogen atom with a methyl group. The water molecule arrangement differs slightly from the one previously reported . However, these two structures are almost isoenergetic, because they have the same number of alanine‐water and water‐water HBs.…”

“…For α‐aminobutyric acid, computed and experimental comparison is less exciting, but acceptable. In any case, present results indicate that our full quantum chemical and bottom‐up modeling is very promising not only for studying the main chain conformation, as was shown for various di‐ and tripeptides where the involved energies are larger, but also for deriving fine details related to the side chains.…”

“…The minimal H‐bonded water network surrounding glycine consists of 13 solvent molecules, Gly · 13H 2 O, Figure . The model was developed maximizing glycine‐water interaction energy with the minimal number of water molecules and considering some intuitive constraints: (a) a water molecule can form two H‐bonds as an acceptor and two as a donor in the optimal coordination geometry; (b) each hydrogen of the ammonium group acts as an H‐bond donor, while each oxygen of the carboxylate group forms two H‐bonds as an acceptor; (c) clusters and wires of water molecules surround amino acids alternating donor/acceptor H‐bonds to realize the highest‐density packing; (d) the bridging water networks should avoid strained cyclic structures; (e) the dipoles of water molecules should align in the opposite direction to the huge dipole of charged amino acid.…”

“…They undoubtedly provide the main contribution to the overall hydration energy of biomolecules (Figure ), since the strength of the direct >CO⋯H 2 O and >N─H⋯OH 2 HBs are of the same magnitude of the H 2 O⋯H 2 O ones . For instance, they are the main stabilizing factor of the polyproline type II helix (PPII) in the unfolded peptide state …”

“…Recently, we reported a protocol to evaluate hydration effects on molecular properties by means of full quantum mechanics methods for atomic interactions along with a bottom‐up approach for the water shell construction around di‐ and tripeptides . Those investigations provided useful information on the intimate solute‐water contacts and in particular, it was shown that hydrophilic interactions among water molecules and peptide polar groups were very important for molecular structures and thermodynamic function predictions.…”