Dr Administrator
Author's posts
Nov 09 2009
Pretty molecular models
And now I leap off into a topic in which I am not properly trained: molecular biology!
You sometimes get the impression that scientists lead dull lives because they over-analyse things, they’ve lost their sense of wonder. The thing is: the more you know, the more you wonder.
One step up from atoms, you find molecules – atoms bound together. Starting things simple, here’s caffeine:
As every chemist kno carbon (C) atoms are black, nitrogen(N) atoms are blue, oxygen(O) atoms are red and hydrogen (H) atoms are white. (Not really but those are their traditional colours in molecular models). Isn’t it beautiful? You can play with an interactive version here. In real life chemistry is more messy than this which is why I’m a physicist rather than a chemist.
The caffeine molecule is about 1 nanometer across, 1 (US) billionth of a meter. To give you a feel for the size of a nanometre: think of a grain of rice – about 1mm across, now imagine a kilometre. Walk your kilometre with the grain of rice, I walk a kilometre in about ten minutes and it takes me past two roundabouts, a gym and a postbox. Now look at you grain of rice again. To a caffeine molecule, a grain of rice is a kilometre wide.
Molecular models of this sort are a representation of reality, the things they miss out are: (1) in real life molecules are not static, they’re jiggling away furiously through the action of thermal energy (2) generally they’re going to be surrounded by solvent molecules (often water, which are also zipping and wiggling around) (3) they’re sort of soft, fuzzy and deformable and different parts of the molecule will be sticky or slippery according to their chemical nature. Ten years ago a good question at any molecular modelling seminar was to ask about the solvent molecules, the usual answer was “there aren’t any” – this usefully puts molecular modellers in their place since we’re rarely interested in molecules without solvent. Perhaps things have moved on since those days.
Life specialises in bigger molecules than caffeine, exquisitely crafted into little machines. And the incredible things is that all of life (humans, mammals, reptiles, birds, snails, bees, tardigrades, sponges, plants, algae, bacteria, fungi, weird bacteria that live in hot underwater vents) share the same 4-letter DNA code, which codes for the same set of 21 amino acids which build all the proteins to make life. Many of the proteins themselves aren’t hugely dissimilar across all the plant and animal kingdoms, particularly those to do with the most basic operations (processing DNA, converting food to energy).
Proteins are strings of amino acids: each different type of protein has a different sequence of amino acids.
Protein molecules typically contain many (a hundred or more) amino acids. The amino acid sequence is known as the primary structure, next up is the secondary structure: alpha-helices and beta-sheets. Different amino acid sequences can produce alpha-helices and beta-sheets that look the same. These structures are represented using “ribbons”:
This is a model of lysozyme, the alpha-helices are shown in red and the beta-sheets are yellow, bits of “random coil” amino acid sequence are shown in green. Lysozyme is about 5 nanometres from one end to the other. You can play with an interactive version here. The amazing thing about proteins is that their 3D structure forms spontaneously and very rapidly when they are synthesised in the cell, this process is known as ‘folding’. Furthermore the folded, or tertiary structure, of the protein is the same every time – it has to be or the protein won’t do it’s job. One of the great challenges in molecular biology is that, despite knowing the amino acid sequence of a protein from the DNA which encodes it, working out the 3D structure is a question of measurement, or comparison with other sequences of known folded structure.
Lysozyme is a physicist’s protein, you can buy it in bottles by the gram. I’ve worked on lysozyme, looking to see how it unfolds on a surface when heated.
You can go see more protein structures on http://proteopedia.org/, the lysozyme model above is 132L. I could play on there for hours…
References
Green, R.J., Hopkinson, I. & Jones, R.A.L. Unfolding and intermolecular association in globular proteins adsorbed at interfaces. Langmuir 15, (1999), 5102-5110.
Oct 31 2009
Bryn Alyn – an autumn walk
Off to Llanferres yesterday for an autumn walk through the woods, along the ridge and back again. You can see the route here:
View Bryn Alyn in a larger map
It’s a variant on a route in “Walking in the Clwydian Range” by Carl Rogers. A tiny domestic detail: whilst walking the Inelegant Gardener carries the guide book, preferring to navigate via prose and I carry the OS map – preferring maps. The track is from a Garmin GPS60, I don’t use it for navigation but to tag my photos with location information for which I’ve written a little program.
We last did this walk in May, but I committed a terrible faux pas: the battery on my camera went flat and for some reason I’d not brought a spare and had deliberately left behind my second camera and my phone (which also has a camera, which is really crap).
Beech trees were definitely the best for autumnal colours, although birch produces an attractive pointillist effect, sycamore seemed best for kicking through.
At the top of the initial climb there is a little bit of limestone pavement, this is most famously found above Malham Cove but it’s nice to find your own little patch.
For reasons I can’t explain I like the stray bits of ironwork left over from old fencing, parts of the Lake District are particularly good for this.
And to top it all off, a cow wearing a ginger wig:
This was one of many cows in a field we passed through, they were fine looking beef cows in a wide range of colours. We also had a “That’s no cow, it’s a bull” moment but I was reassured by remembering vaguely someone saying that you’re okay in a field with a load of cows and a bull because the last thing on the bull’s mind is going to be you. If this isn’t actually true then I’d prefer to be left in ignorance, if you don’t mind.
Oct 30 2009
Professor Nutt and the classification of harm through the misuse of drugs
The sacking of Professor Nutt (now ex-head of the Advisory Council on the Misuse of Drugs) by the Home Secretary Alan Johnson, has been in the news today. The immediate cause of his sacking appears to have been this recently published paper which was originally presented as the “2009 Eve Saville Memorial Lecture” at the Centre for Crime and Justice Studies at King’s College in July 2009. The lecture appears to have been a policy discussion based in part on his classification of relative drug harm which was first published in The Lancet in 2007:
Development of a rational scale to assess the harm of drugs of potential misuse, David Nutt, Leslie A King, William Saulsbury, Colin Blakemore, The Lancet, vol. 369, (2007), p1047-1053.
This is done iteratively using what is called a ‘delphic process’, the experts make their initial numerical assessments independently in an initial round, but can then modify those assessments once they have seen and discussed the assessments made by others. Once they have reached some pre-determined finishing criteria they combine the average scores for each area to produce an overall measure of harm. They are pre-warned of the substances in question so they can go read up on them. The rankings of the two separate groups appeared to be very much in agreement. The resulting mean harm scores for the twenty substances are shown in the following graph:
The interesting thing about this group is that tobacco and alcohol (which I’m currently enjoying in the form of fine Chardonnay) are found in the middle of the range, below heroin and cocaine but above cannabis and Ectasy. A statement which in part has earnt Professor Nutt his dismissal.
Now you could argue that “The Lancet” paper is flawed, and Professor Nutt makes suggests for improvements in methodology, but the thing is: there is no competition. Current drug classifications into A, B and C are not made on an assessment of harm based on any published or transparent criteria. If Alan Johnson wants to argue that Professor Nutt is wrong on his evaluation of the relative harm of drugs he should do so on the basis of a transparent evaluation process not because he just doesn’t like the advice he’s been given.
Though I have not focussed on it in this post, the Eve Saville lecture includes this assessment of harm along with a discussion of other issues including the media reporting of deaths through drug misuse. It does also include some support for elements of government policy on drugs, in particular he says:
One thing this government has done extremely well in the last ten years is to cut away much of the moral argument about drug treatments. They have moved in the direction of improving access to harm reduction treatments, an approach that, I think, is wholly endorsed by the scientifi c community and by the medical profession.
Update
1st November 2010: Professor Nutt has published an improved version of this study in The Lancet (pdf), the process used is a little different and an attempt has been made to improve the relative weight given to different harms. This revised study finds that heroin, crack cocaine and metamfetamine most harmful to individual users and alcohol, heroin and crack cocaine most harmful to others.
About
I've worked as a scientist for the last 30 years, at various universities, a large home and personal care company, a startup in Liverpool called The Sensible Code Company (formerly ScraperWiki Ltd), GBG and now as a consultant in data science.
I write about:
* the books I have read, typically science and history (or both), partly as a reminder to myself and partly as a review;
* science, things I have done or things I find interesting;
* technology, programming and gadgets;
politics, and current affairs;
* ...and other stuff as it takes my fancy - holidays, photographs and things I want to remember.