Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 22, Issue 8, Pages 2672-2681Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201503973
Keywords
acetylcholinesterase; density functional calculations; drug design; hydrogen bonds; quantum chemistry
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Funding
- Swedish Research Council
- Umea University
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Molecular recognition events in biological systems are driven by non-covalent interactions between interacting species. Here, we have studied hydrogen bonds of the CHY type involving electron-deficient CH donors using dispersion-corrected density functional theory (DFT) calculations applied to acetylcholinesterase-ligand complexes. The strengths of CHY interactions activated by a proximal cation were considerably strong; comparable to or greater than those of classical hydrogen bonds. Significant differences in the energetic components compared to classical hydrogen bonds and non-activated CHY interactions were observed. Comparison between DFT and molecular mechanics calculations showed that common force fields could not reproduce the interaction energy values of the studied hydrogen bonds. The presented results highlight the importance of considering CHY interactions when analysing protein-ligand complexes, call for a review of current force fields, and opens up possibilities for the development of improved design tools for drug discovery.
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