Imperial College London

Henry Rzepa

[Derek
Lowe](http://blogs.sciencemag.org/pipeline/archives/2017/05/24/a-new-factor-in-protein-folding)
highlights a recent article\[cite\]10.1002/anie.201702626\[/cite\]
postulating CH⋅⋅⋅π interactions in proteins. Here I report a quick check
using the small molecule crystal structure database (CSD).

The search query
(DOI: [10.14469/hpc/2594](https://doi.org/10.14469/hpc/2594)) is shown
below.![](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/150.jpg){.aligncenter
.size-full .wp-image-18400 decoding="async" width="450"
srcset="https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/150.jpg 946w, https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/150-300x238.jpg 300w, https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/150-768x611.jpg 768w"
sizes="(max-width: 946px) 100vw, 946px"}

1.  The distance refers to that between the (normalised) position of a
    hydrogen on a 4-coordinated carbon atom and the centroid of a
    carbonyl group substituted with R=C or H. 
2.  The angle is that subtended at the centroid. An approach orthogonal
    to the axis of the carbonyl group will have a value of 1.0 for the
    sine.
3.  The torsion relates to the angle between the H...centroid and C-R
    vectors. The absolute value is constrained to 70-110° to filter only
    approaches towards the π-system of the carbonyl.
4.  The search is further restricted to no disorder, no errors and R \<
    0.05. 

![](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/152-1024x637.jpg){.aligncenter
.size-large .wp-image-18402 loading="lazy" decoding="async" width="450"
height="280"
srcset="https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/152-1024x637.jpg 1024w, https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/152-300x187.jpg 300w, https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/152-768x478.jpg 768w, https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/152.jpg 1546w"
sizes="(max-width: 450px) 100vw, 450px"}

The two most interesting hits, both revealing short distances and
\~orthogonal approaches to the π-system are:

- HIKWEF [10.5517/cc11m594](https://dx.doi.org/10.5517/cc11m594), 2.045Å
- YAKNIB [10.5517/ccxkyx9](https://dx.doi.org/10.5517/ccxkyx9), 2.274Å

Remember however that such "outliers" must always be carefully
inspected. There are more numerous interactions in the region 2.4-2.6Å
with a sine(angle) of \>0.9 and and a close orthogonal approach to the
π-system (green dots) which probably qualify for the title above. There
seem many interesting but still putative small-molecule candidates for
this proposed interaction postulated for proteins. 

**Postscript:**  Here the results of the search above with R= any of
H,C,N,O,F,Cl up to values of the distance \<2.4Å, which show a range of
interesting (green)
points.![](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/153-1024x652.jpg){.aligncenter
.size-large .wp-image-18404 loading="lazy" decoding="async" width="450"
height="287"
srcset="https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/153-1024x652.jpg 1024w, https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/153-300x191.jpg 300w, https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/153-768x489.jpg 768w, https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2017/05/153.jpg 1562w"
sizes="(max-width: 450px) 100vw, 450px"}

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rel="author"}
:::


Derek Lowe highlights a recent article[cite]10.1002/anie.201702626[/cite] postulating CH⋅⋅⋅π interactions in proteins. Here I report a quick check using the small molecule crystal structure database (CSD).  The search query (DOI: 10.14469/hpc/2594) is shown below.

Messaggi di Rogue Scholar

CH⋅⋅⋅π Interactions between methyl and carbonyl groups in proteins: a small molecule check.