Accurate ab initio study on the hydrogen-bond pairs in protein secondary structures

作者：Wang Zhi Xiang; Wu Chun; Lei Hongxing; Duan Yong^*

来源：Journal of Chemical Theory and Computation, 2007, 3(4): 1527-1537.

DOI：10.1021/ct700021f

Ab initio calculations up to the MP2/aug-cc-pVQZ//MP2/6-311+G** level have been carried out to characterize the four patterns of hydrogen-bond (H-bond) pairs in protein secondary structures. The unblocked and methyl-blocked glycine dipeptide dimers were arranged to model the H-bond pairs in alpha-helix (alpha HH) and antiparallel (A beta beta-C-5 and A beta beta-C-7) and parallel beta-sheet (P beta beta) secondary structures. The study uncovers that, in addition to the primary CO center dot center dot center dot NH H-bonds and the crossing secondary interactions, the CH center dot center dot center dot OC H-bonds and the tertiary effect (as we call it) also contribute substantially. The tertiary effect is due to the interpolarization between the donor and acceptor of a H-bond. This effect, which enhances the dipole-dipole interactions between two nearby H-bonds, stabilizes the beta-sheet-like but destabilizes the helix-like H-bond pairs. The MP2 binding energies of the complexes were further refined by extrapolating to the complete basis set limit (CBS) according to Truhlar and co-workers and by a three-basis-set-based method. The best extrapolated CBS(aD-aT-aQ) binding energies of the unblocked dimers are -13.1 (alpha HH), -11.3 (A beta beta-C-5), -19.2 (A beta beta-C-7), and -14.8 kcal/mol (P beta beta). For the methyl-blocked counterparts, the best extrapolated CBS(D-T-Q) binding energies are -14.8, -13.4, -20.8, and -16.7 kcal/mol, respectively. The interactions in the parallel beta conformations are very close to the averages of the C-5 and C-7 antiparallel beta conformations, and both are stronger than the helical dimers. Because the additive force fields are unable to account for the tertiary effect owing to the lack of polarization, all examined additive force fields significantly overestimate the interaction energies of the helix conformations relative to the beta-sheet conformations. Notably, the agreement between molecular mechanical and quantum mechanical binding energies is improved after turning on the polarization. The study provides reference ab initio structures and binding energies for characterizing the backbone H-bonds of the protein secondary structures, which can be used for the parametrization of empirical molecular mechanics force fields.

• 出版日期2007-8