Posts Tagged ‘high energy species’

Why are α-helices in proteins mostly right handed?

Saturday, April 9th, 2011

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 prize) when in a famous paper[1] in 1951 he suggested a mechanism that involved (inter alia) the formation of what he termed α-helices. Jack Dunitz in 2001[2] wrote a must-read article[3] on the topic of “Pauling’s Left-handed α-helix” (it is now known to be right handed). I thought I would revisit this famous example with a calculation of my own and here I have used the ωB97XD/6-311G(d,p) DFT procedure[4] to calculate some of the energy components of a small helix comprising (ala)6 in both left and right handed form.

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References

  1. L. Pauling, R.B. Corey, and H.R. Branson, "The structure of proteins: Two hydrogen-bonded helical configurations of the polypeptide chain", Proceedings of the National Academy of Sciences, vol. 37, pp. 205-211, 1951. http://dx.doi.org/10.1073/pnas.37.4.205
  2. J.D. Dunitz, "Pauling's Left-Handed α-Helix", Angewandte Chemie International Edition, vol. 40, pp. 4167-4173, 2001. http://dx.doi.org/10.1002/1521-3773(20011119)40:22<4167::AID-ANIE4167>3.0.CO;2-Q
  3. K.S. Thanthiriwatte, E.G. Hohenstein, L.A. Burns, and C.D. Sherrill, "Assessment of the Performance of DFT and DFT-D Methods for Describing Distance Dependence of Hydrogen-Bonded Interactions", Journal of Chemical Theory and Computation, vol. 7, pp. 88-96, 2010. http://dx.doi.org/10.1021/ct100469b

The Cyclol Hypothesis for protein structure: castles in the air.

Monday, April 4th, 2011

Most scientific theories emerge slowly, over decades, but others emerge fully formed virtually overnight as it were (think Einstein in 1905). A third category is the supernova type, burning brightly for a short while, but then vanishing (almost) without trace shortly thereafter. The structure of DNA (of which I have blogged elsewhere) belongs to the second class, whilst one of the brightest (and now entirely forgotten) examples of the supernova type concerns the structure of proteins. In 1936, it must have seemed a sure bet that the first person to come up with a successful theory of the origins of the (non-random) relatively rigid structure of proteins would inevitably win a Nobel prize. Of course this did happen for that other biologically important system, DNA, some 17 years later. Compelling structures for larger molecules providing reliable atom-atom distances based on crystallography were still in the future in 1936, and so structural theories contained a fair element of speculation and hopefully inspired guesswork (much as cosmological theories appear to have nowadays!).

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