{"id":3326,"date":"2011-01-01T20:23:14","date_gmt":"2011-01-01T19:23:14","guid":{"rendered":"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=3326"},"modified":"2023-09-16T18:14:35","modified_gmt":"2023-09-16T17:14:35","slug":"a-comparison-of-left-and-right-handed-dna-double-helix-models","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=3326","title":{"rendered":"A comparison of left and right handed DNA double-helix models."},"content":{"rendered":"
\n

When Watson and Crick (WC) constructed their famous 3D model for DNA, they had to decide whether to make the double helix left or right handed. They chose a right-handed turn, on the grounds that their attempts at left-handed models all “violated permissible van der Waals contacts<\/em>“. No details of what these might have been were given in their original full article<\/a> (or the particular base-pairs which led to the observation).\u00a0This follow-up<\/a> to my earlier post explores this aspect, using a computer model.<\/p>\n

\"\"<\/a>

One half of a (CGCG) DNA strand<\/p><\/div>\n

The DNA model<\/a> used here is shown above; in shorthand it is d(CGCG)2<\/sub>. A crystal structure<\/a> reveals it to form a (non-Watson-Crick) left-handed helix. If you open the 3D model below (based on a \u03c9B97XD\/6-31G(d)\/SCRF=water optimisation), some of the short van der Waals contacts are measured. Most are around 2.25\u00c5 and the shortest is 2.1\u00c5. It is worth noting that WC note in their article that a distance of 2.1\u00c5 for the B-form is acceptable (p92, bottom) and not a violation.\u00a0All twelve hydrogen bond lengths H…O or H…N are normal, with lengths around 1.8\u00c5. Given that a H…H distance is at its most attractive<\/strong> at ~2.4\u00c5, and plenty of H…H distances of ~2.1\u00c5 are known from the crystal structures of organic molecules, one might conclude that (for the CG base pair), their hypothesis that the Z-form could be eliminated was wrong.<\/p>\n

\"\"

The DNA duplex d(CGCG) showing a left handed helix with short H...H contacts shown. Click for 3D<\/p><\/div>But might the original WC-right handed form for this system be at least competitive? There is one H…H of 2.05\u00c5 and quite a few at ~2.5\u00c5 (3D model below). The “violation” of van der Waals contacts is if anything slightly worse than with the left-handed helix. The total difference in the dispersion energy is a rather astonishing ~12 kcal\/mol in favour of the Z-form<\/strong>. I will update this post (as a comment) when the relative free energies of the two forms are available (this calculation takes a while<\/a>), but there is little doubt that the Z-form is indeed the more stable.<\/p>\n

\"\"

The DNA duplex d(CGCG) showing a right handed helix with short H...H contacts shown. Click for 3D<\/p><\/div>What can also be said about the Watson-Crick right handed form is that the hydrogen bonding is not so optimal. One of the twelve interactions between a (terminal) CG pair has some signs of being “unzipped<\/em>“, with an N-H…O=C distance of ~1.9\u00c5 (there is no sign of similar unzipping in the Z-form). One must wonder whether this difference in the Z- and B-helices for the CG pair has been exploited in nature.<\/p>\n

 <\/p>\n

One crucial aspect of DNA is the local conformation about the bond connecting the base and the ribose, N9<\/sub>-C8 <\/sub>in the diagram below(green arrow).<\/p>\n

\"\"

Conformation of the base-ribose unit<\/p><\/div>An analysis of this bond can be expressed<\/a> in terms of NBO theory. This clearly shows a strong interaction energy (E2) between the lone pair on N9<\/sub> and the C8<\/sub>-O4<\/sub> antibonding orbital of 13.3 kcal\/mol, a classical anomeric effect<\/a>in fact.\u00a0In this case, it promotes the local conformation of this unit, which has a significant effect on the final model.<\/p>\n

What else can analysis of the wavefunction tell us? Well, curiously, the optical rotation of this particular small oligomer has never been reported in the literature, and an intriguing question is whether it might have proved useful to distinguish between B- and Z-forms of the duplex? To do this, one needs a reasonably reliable way of computing [\u03b1]D<\/sub> for both<\/strong> isomers. This is because optical rotations are not reliably additive, and it is difficult to estimate them accurately based purely on the fragments present in the molecule. In 2011, is is now perfectly possible to calculate this quantity quantum mechanically, even for 250 atoms, using a reasonable basis set and making allowance for solvation (which is known to affect the calculated rotation). The values (CAM-B3LYP\/6-31G(d)\/SCRF=water) for the Z-isomer are 66\u00b0 and 32\u00b0 for the B-isomer. Of course the model is not complete, lacking a counterion for the phosphate and explicit water molecules, but even so, it might appear that the reason optical rotations are not reported is that they truly are not useful!<\/p>\n

\n

Acknowledgments<\/h4>\n

This post has been cross-posted in PDF format at Authorea<\/a>.<\/p>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

When Watson and Crick (WC) constructed their famous 3D model for DNA, they had to decide whether to make the double helix left or right handed. They chose a right-handed turn, on the grounds that their attempts at left-handed models all “violated permissible van der Waals contacts“. 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Plenty are on show in Watson and Crick's famous 1953 article on the structure of DNA but often with the tersest of explanations. Take for example their statement \"Both chains follow right-handed helices\". Where did that come from? This post will explore the subtle implications\u2026","rel":"","context":"In "Interesting chemistry"","block_context":{"text":"Interesting chemistry","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=4"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2010\/12\/tartrate.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":3802,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=3802","url_meta":{"origin":3326,"position":1},"title":"Why are \u03b1-helices in proteins mostly right handed?","author":"Henry Rzepa","date":"April 9, 2011","format":false,"excerpt":"Understanding why and how proteins fold continues to be a grand challenge in science. I have described how Wrinch in 1936 made a bold proposal for the mechanism, which however flew in the face of much of then known chemistry. Linus Pauling took most of the credit (and a Nobel\u2026","rel":"","context":"In "Interesting chemistry"","block_context":{"text":"Interesting chemistry","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=4"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2011\/04\/left-n.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":4089,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4089","url_meta":{"origin":3326,"position":2},"title":"The inner secrets of the DNA structure.","author":"Henry Rzepa","date":"May 18, 2011","format":false,"excerpt":"In earlier posts, I alluded to what might make DNA wind into a left or a right-handed helix. Here I switch the magnification of our structural microscope up a notch to take a look at some more inner secrets. The 3D coordinates of this fragment were obtained by taking a\u2026","rel":"","context":"In "General"","block_context":{"text":"General","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2011\/05\/CGCG.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":3621,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=3621","url_meta":{"origin":3326,"position":3},"title":"The thermodynamic energies of left and right handed DNA.","author":"Henry Rzepa","date":"March 5, 2011","format":false,"excerpt":"In this earlier post, I noted some aspects of the calculated structures of both Z- and B-DNA duplexes. These calculations involved optimising the positions of around 250-254 atoms, for d(CGCG)2 and d(ATAT)2, an undertaking which has taken about two months of computer time! The geometries are finally optimised to the\u2026","rel":"","context":"In "Interesting chemistry"","block_context":{"text":"Interesting chemistry","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=4"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":3443,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=3443","url_meta":{"origin":3326,"position":4},"title":"Is there a difference between a scientific blog and scientific journal?","author":"Henry Rzepa","date":"January 14, 2011","format":false,"excerpt":"In my blogroll, I link to Tim Gowers' blog. He is a very eminent mathematician, and so it is interesting to see what motivates him to write a blog about mathematics. This latest post goes a large way to explaining why. He starts by speculating about the features of some\u2026","rel":"","context":"In "General"","block_context":{"text":"General","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":4688,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4688","url_meta":{"origin":3326,"position":5},"title":"Breakdowns in communication: the two cultures","author":"Henry Rzepa","date":"August 2, 2011","format":false,"excerpt":"In his famous lecture in 1959, C. P. Snow wrote about the breakdown in communications between\u00a0the \"two cultures\" of modern\u00a0society \u2014 the\u00a0sciences and the\u00a0humanities (arts). That was then. This is now, and the occasion of my visit to a spectacular \"city of arts and sciences complex\" in Europe. An un-missable\u2026","rel":"","context":"In "General"","block_context":{"text":"General","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2011\/08\/CGCG.jpg?resize=350%2C200","width":350,"height":200},"classes":[]}],"jetpack_likes_enabled":false,"authors":[{"term_id":2661,"user_id":1,"is_guest":0,"slug":"admin","display_name":"Henry Rzepa","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/897b6740f7f599bca7942cdf7d7914af5988937ae0e3869ab09aebb87f26a731?s=96&d=blank&r=g","0":null,"1":"","2":"","3":"","4":"","5":"","6":"","7":"","8":""}],"_links":{"self":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/3326","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=3326"}],"version-history":[{"count":4,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/3326\/revisions"}],"predecessor-version":[{"id":26459,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/3326\/revisions\/26459"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=3326"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=3326"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=3326"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=3326"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}