The title comes from the abstract of an article[1] analysing why Biotin (vitamin B7) is such a strong and effective binder to proteins, with a free energy of (non-covalent) binding approaching 21 kcal/mol. The author argues that an accumulation of both CH-π and CH-O together with more classical hydrogen bonds and augmented by a sulfur centered hydrogen bond, oxyanion holes and water solvation, accounts for this large binding energy.
Here, I thought I would present a visualisation of the surroundings of biotin using the method of NCI (non-covalent-interaction) analysis, which looks at the behaviour of the electron density in the “weak” (i.e. non-covalent) regions of the biotin. This provides a more objective measure of the important interactions, independent of what we might consider important by virtue of having labels attached (such as e.g. “hydrogen bond”).
Do go ahead and load the 3D surface. You should particularly explore the CH-π regions and note that they are not necessarily associated with a particular CH bond, but with several of these combining to form an interaction with an aromatic π region.
What might emerge is the realisation that binding interactions are not always between specific atoms as in classical hydrogen “bonds”, but also constitute “stabilising regions” between the ligand and the protein. You will probably spot several of these regions that are not actually listed in the article itself.[1] I suggest that we do not refer to CH…π bonds such as in the quoted title of this post but instead as CH…π regions.
It would be great if the entire complex could be subjected to an NCI analysis. Wavefunctions for >2000 atoms can be obtained nowadays, but it would require a bit of work to ensure the density can be computed accurately enough and at high enough cubic resolution to be useful in the context of NCI analysis.
This blog has DOI: 10.14469/hpc/9984
In the mid to late 1990s as the Web developed, it was becoming more obvious…
I have written a few times about the so-called "anomeric effect", which relates to stereoelectronic…
The recent release of the DataCite Data Citation corpus, which has the stated aim of…
Following on from my template exploration of the Wilkinson hydrogenation catalyst, I now repeat this…
In the late 1980s, as I recollected here the equipment needed for real time molecular…
On 24th January 1984, the Macintosh computer was released, as all the media are informing…