Large-Scale Analysis of Hydrogen Bond Interaction Patterns in Protein-Ligand Interfaces

Journal of Medicinal Chemistry
Eva NittingerMatthias Rarey

Abstract

Protein-ligand interactions are the fundamental basis for molecular design in pharmaceutical research, biocatalysis, and agrochemical development. Especially hydrogen bonds are known to have special geometric requirements and therefore deserve a detailed analysis. In modeling approaches a more general description of hydrogen bond geometries, using distance and directionality, is applied. A first study of their geometries was performed based on 15 protein structures in 1982. Currently there are about 95 000 protein-ligand structures available in the PDB, providing a solid foundation for a new large-scale statistical analysis. Here, we report a comprehensive investigation of geometric and functional properties of hydrogen bonds. Out of 22 defined functional groups, eight are fully in accordance with theoretical predictions while 14 show variations from expected values. On the basis of these results, we derived interaction geometries to improve current computational models. It is expected that these observations will be useful in designing new chemical structures for biological applications.

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Citations

Feb 21, 2019·ChemMedChem·Moira RachmanGyörgy M Keserű
Apr 17, 2020·Nucleic Acids Research·Katrin Schöning-StierandMatthias Rarey
Jan 9, 2018·MedChemComm·Renato Ferreira de Freitas, Matthieu Schapira
Nov 7, 2019·BMC Complementary and Alternative Medicine·Andrea Isabel Trujillo-CorreaMarlen Martinez-Gutierrez
Feb 23, 2020·Proceedings of the National Academy of Sciences of the United States of America·Aya NarunskyNir Ben-Tal
Dec 10, 2019·Computational and Mathematical Methods in Medicine·Wei WangJunwei Huang
Dec 24, 2018·European Journal of Medicinal Chemistry·Kai SommerMatthias Rarey
Jan 4, 2021·Current Opinion in Structural Biology·Tushar ModiSefika Banu Ozkan
Nov 20, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Roberto Pestana-NoblesJuvenal Yosa
Nov 17, 2020·Journal of Chemical Information and Modeling·Patrick PennerMatthias Rarey
Dec 2, 2020·Journal of Chemical Information and Modeling·Florian FlachsenbergMatthias Rarey
May 24, 2019·Journal of Medicinal Chemistry·Nicolas K ShinadaPeter Schmidtke
Jul 24, 2018·Journal of Chemical Information and Modeling·Eva NittingerMatthias Rarey
Jul 12, 2019·Journal of Chemical Information and Modeling·Zhijian XuWeiliang Zhu
Nov 16, 2019·Journal of Medicinal Chemistry·Bernd KuhnOliver Korb
Sep 12, 2017·Journal of Chemical Information and Modeling·Therese InhesterMatthias Rarey
Feb 28, 2020·Journal of Chemical Theory and Computation·Diogo Santos-Martins, Stefano Forli

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