B-H⋯π and C-H⋯π interactions in protein-ligand complexes: carbonic anhydrase II inhibition by carborane sulfonamides

0567034 - ÚOCHB 2024 RIV GB eng J - Journal Article
Fanfrlík, Jindřich - Brynda, Jiří - Kugler, Michael - Lepšík, Martin - Pospíšilová, Klára - Holub, Josef - Hnyk, Drahomír - Nekvinda, Jan - Grüner, Bohumír - Řezáčová, Pavlína
B-H⋯π and C-H⋯π interactions in protein-ligand complexes: carbonic anhydrase II inhibition by carborane sulfonamides.
Physical Chemistry Chemical Physics. Roč. 25, č. 3 (2023), s. 1728-1733. ISSN 1463-9076. E-ISSN 1463-9084
R&D Projects: GA MŠMT(CZ) EF16_019/0000729; GA MŠMT LX22NPO5102; GA ČR(CZ) GA21-14409S
Institutional support: RVO:61388963 ; RVO:61388980
Keywords : ⋯π * hydrogen bond * dispersion
OECD category: Physical chemistry; Inorganic and nuclear chemistry (UACH-T)
Impact factor: 3.3, year: 2022
Method of publishing: Open access
https://doi.org/10.1039/D2CP04673C

Among non-covalent interactions, B-H⋯π and C-H⋯π hydrogen bonding is rather weak and less studied. Nevertheless, since both can affect the energetics of protein-ligand binding, their understanding is an important prerequisite for reliable predictions of affinities. Through a combination of high-resolution X-ray crystallography and quantum-chemical calculations on carbonic anhydrase II/carborane-based inhibitor systems, this paper provides the first example of B-H⋯π hydrogen bonding in a protein-ligand complex. It shows that the B-H⋯π interaction is stabilized by dispersion, followed by electrostatics. Furthermore, it demonstrates that the similar C-H⋯π interaction is twice as strong, with a slightly smaller contribution of dispersion and a slightly higher contribution of electrostatics. Such a detailed insight will facilitate the rational design of future protein ligands, controlling these types of non-covalent interactions.
Permanent Link: https://hdl.handle.net/11104/0338302


Research data: PDB Worldwide, PDB Worldwide