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

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.

  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. 

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

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.

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2 Responses to “CH⋅⋅⋅π Interactions between methyl and carbonyl groups in proteins: a small molecule check.”

  1. shant shahbazian says:

    Indeed interesting…

  2. Henry Rzepa says:

    Here are plots with OH and NH replacing CH interactions.

    Note that sine(angle) < 0.7 or so are approaching the oxygen or nitrogen lone pairs rather than necessarily the π-system. Focus again on the green dots.

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