5FOQ

Acetylcholinesterase in complex with C7653

Summary for 5FOQ

• Entry DOI: 10.2210/pdb5foq/pdb
• Related: 5FPP 5FPQ
• Descriptor: ACETYLCHOLINESTERASE, 2-acetamido-2-deoxy-beta-D-glucopyranose, 2-(2,4-dichlorophenoxy)-N-[4-(1-piperidinylmethyl)phenyl]acetamide, ... (6 entities in total)
• Functional Keywords: hydrolase, signaling protein, quantum chemistry, density functional theory, drug design
• Biological source: MUS MUSCULUS (HOUSE MOUSE)
• Total number of polymer chains: 2
• Total formula weight: 122695.15

Authors

Berg, L.,Mishra, B.K.,Andersson, D.C.,Ekstrom, F.,Linusson, A. (deposition date: 2015-11-25, release date: 2016-03-02, Last modification date: 2024-10-23)

Primary citation

Berg, L.,Mishra, B.K.,Andersson, C.D.,Ekstrom, F.,Linusson, A.
The Nature of Activated Non-Classical Hydrogen Bonds: A Case Study on Acetylcholinesterase-Ligand Complexes.
Chemistry, 22:2672-, 2016

PubMed Abstract: Molecular recognition events in biological systems are driven by non-covalent interactions between interacting species. Here, we have studied hydrogen bonds of the CH⋅⋅⋅Y type involving electron-deficient CH donors using dispersion-corrected density functional theory (DFT) calculations applied to acetylcholinesterase-ligand complexes. The strengths of CH⋅⋅⋅Y 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 CH⋅⋅⋅Y 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 CH⋅⋅⋅Y 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.

PubMed: 26751405
DOI: 10.1002/CHEM.201503973

Experimental method

X-RAY DIFFRACTION (2.3 Å)