A friend of mine just returned from a conference in New York organised by Schrodinger, and I have to say that Schrodinger really seems to be poised to be the one-stop shop for all things computational.
They already have some great programs in their Maestro suite, including Glide for docking, which you find folks in industry using more and more these days. In their next revisions, they are going to introduce a program named PrimeX for doing crystallography, which will perform analysis similar to CNS, which will be groovy if it brings such analysis to the desktop. They are also going to introduce electron-density fitting for loop refinement in proteins. Right now, loop refinement of, say a 10 residue loop takes forever. But with PrimeX and friends, one can have constraints effected by electron density to restrict conformational searching, thus greatly speeding up the process.
Other products include the very impressive new Glide XP docking protocol. I have been glued to their site ever since they published their admirable paper in 2006. I have already written about the capabilities of GlideXP. This is really the best of computational chemistry applied to docking, where you find chemists trying to include as many experimental parameters as they can in a program. Schrodinger is definitely one company whose chemists have a firm and steady hand on experimental variables.
A very important development is going to be the interfacing of William Jorgensen's MCPRO, a program for doing free energy perturbation (FEP) calculations. FEP calculations are as close as you can come to accurately reproducing experimental binding free energies, one of the holy grails of computational methodology. While GlideXP astoundingly claims to also be able to do that, it would be super to have a GUI and easy operability for a good FEP program at your fingertips. Admittedly, FEP works only for ligand which differ little in their structure (eg. Me vs H). But that's also the phenomenon which we understand the least, how "similar" ligands can have great differences in binding affinity, something which FEP should help us understand.
Other improvements will include better parameters in standard docking, and a new force field, OPLS 2008, which will be "better than MMFF". Considering that the force behind this field is Tom Halgren, the same guy who meticulously crafted MMFF, I would be looking forward to it. There is also talk of a new MD program comparable to Gromacs, AMBER etc. which can do millisecond MD efficiently. That would probably complete the list of capabilities in one program that almost any computational chemist could want.
What I like best about Schrodinger is that it has people at its helm who are among the best that computational chemistry has to offer, most importantly Richard Friesner and Tom Halgren. Looking at their papers, it's clear that like ideal computational chemists, they thoroughly understand experimental data, and clearly know what the limitations of their programs are.
Field of Science
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Change of address1 year ago in Variety of Life
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Change of address1 year ago in Catalogue of Organisms
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Earth Day: Pogo and our responsibility1 year ago in Doc Madhattan
Decide how you want to die...
...by scurvy or DNA damage. Hopefully, none.
An interesting study has appeared in the British Journal of Nutrition (2007, 97, p.639), which seems to say what many of us may have suspected; that nature knows best. The study investigates the effect of Vitamin C as an antioxidant when taken alone in the form of pills, or as a component of oranges or orange juice.
The study made volunteers drink Vit C water, orange juice, and sugar water as a control. After the Vit C levels in all the volunteers' blood were equalised, samples were taken and were exposed to hydrogen peroxide, a known DNA damage agent. Surprisingly, the levels of DNA damage were much lower in the orange juice-fed volunteers than the Vit C water volunteers.
I have not had access to the full paper, but the authors conjecture that it may be the other substances in oranges which protect against DNA damage. As I see it, these other substances may be acting as "sacrificial" molecules, themselves getting oxidised and thereby protecting both DNA and Vit C.
Actually, these results should not be surprising. Nature has evolved intricate packages of chemicals that play roles in organisms. Oranges are not just containers for holding Vit C and other compounds, but intricate systems in which there is an essential synergistic interplay of all these substances as well as their container. Taking one out of context creates the same problems as when politicians take words out of contexts. As in many aspects of of nature, the whole is much more than the sum of the parts. In light of this, I sometimes wonder how we have so many effective drugs which are isolated from natural sources and used separately. But then, it's not perfect, is it? Think of how many side effects they have, and this may well be because you are not providing a holistic environment for them to act. Sometimes the leaf is really better than the pill. Validation for old Ayurveda and herbal medicine?
Next time, maybe we can think twice before we substitute a Vitamin tablet for its natural source.
An interesting study has appeared in the British Journal of Nutrition (2007, 97, p.639), which seems to say what many of us may have suspected; that nature knows best. The study investigates the effect of Vitamin C as an antioxidant when taken alone in the form of pills, or as a component of oranges or orange juice.
The study made volunteers drink Vit C water, orange juice, and sugar water as a control. After the Vit C levels in all the volunteers' blood were equalised, samples were taken and were exposed to hydrogen peroxide, a known DNA damage agent. Surprisingly, the levels of DNA damage were much lower in the orange juice-fed volunteers than the Vit C water volunteers.
I have not had access to the full paper, but the authors conjecture that it may be the other substances in oranges which protect against DNA damage. As I see it, these other substances may be acting as "sacrificial" molecules, themselves getting oxidised and thereby protecting both DNA and Vit C.
Actually, these results should not be surprising. Nature has evolved intricate packages of chemicals that play roles in organisms. Oranges are not just containers for holding Vit C and other compounds, but intricate systems in which there is an essential synergistic interplay of all these substances as well as their container. Taking one out of context creates the same problems as when politicians take words out of contexts. As in many aspects of of nature, the whole is much more than the sum of the parts. In light of this, I sometimes wonder how we have so many effective drugs which are isolated from natural sources and used separately. But then, it's not perfect, is it? Think of how many side effects they have, and this may well be because you are not providing a holistic environment for them to act. Sometimes the leaf is really better than the pill. Validation for old Ayurveda and herbal medicine?
Next time, maybe we can think twice before we substitute a Vitamin tablet for its natural source.
Analogies between analogies: The character of Stan Ulam
Derek's post about metaphors and analogies reminded me of a quote by a remarkable mathematician whose name is known only to aficionados now, but who stands in the front rank of brilliant mathematicians and physicists of the twentieth century- Stanislaw Ulam. Here's a quote from him about analogies:
Ulam was born in Poland and grew up in a romantic time in the 20s and 30s, when great discoveries in mathematics and physics were being made in small, enchanting roadside cafes by small groups of people working intensely together. One of those, the Scottish Cafe in Lwow, Poland, was a focal point for meeting of great minds, the best pure mathematicians in Europe. Equations used to be scribbled on tables there, and the waiters were told never to erase them. Marathon sessions used to be common, fueled by black coffee, and interrupted only by occasional meals and trips to the bathroom; one non-stop session lasted 17 hours. The mathematician Rota said this about Ulam's fascinating mind:
After coming to the US, Ulam was secretly invited to join the Manhattan Project in Los Alamos, where he was known to be a problem solver and jovial team worker. In Los Alamos, he tried to recreate the idyllic atmosphere of his young years in Europe by installing a coffee machine outside his office where scientists could talk shop. You can get to see Ulam in The Day after Trinity. Here is a photo of three prodigies from those days, (From L to R) Ulam, Richard Feynman, and John Von Neumann
While at Los Alamos, Ulam made what was probably the most important contribution of his career- the Monte Carlo method, a way of calculating the result of complex processes through random numbers. This method is now so important and deep-rooted in physics, chemistry, and engineering, that many students have forgotten that somebody invented it. The method is now implemented as a black box in many computer programs, such as those which I use for calculating the structure of organic molecules, and so people tend to sometimes use it without knowing that they are using it.
In 1946, Ulam suffered an attack of encephalitis; he could not remember events after the attack, and after the operation, federal agents asked him questions to make sure that he may not have given away atomic secrets during his loss of recollection. After the operation, Ulam seemed to some to become even more brilliant than he had been before.
However, Ulam probably became best-known to a greater audience through his participation in the development of the hydrogen bomb. After the war, he and fellow scientist Cornelius Everett embarked on a series of tedious calculations to prove that the then accepted and widely touted design of the hydrogen bomb would not work. This was a significant result, as President Harry Truman had been earlier prodded to announce a crash effort to develop the bomb based on this design. WIthin a short time however, Ulam came to the essential breakthrough that encouraged the infamous Edward Teller to develop the most widely used design of the h-bomb. The breakthrough involved separating the fission and fusion parts of the weapons, and using compression from the fission bomb to activate the fusion bomb. After this design was invented, everybody assumed that the Soviets were doing it too, and the program was purused with vigour. Every country afterwards that developed thermonuclear weapons has used this so-called "Teller-Ulam" design or a variant of it.
The imperious Teller essentially took much of the credit for the invention, and later tried to expunge Ulam's name from that part of history. Hans Bethe liked to joke that Ulam was really the "father of the h-bomb" while Teller was the mother since he carried the baby for so long. Ulam for his own part, an unassuming and docile man, stayed away from these disputes, when he rightly could have done more for asserting his claim to fame. Ulam and Teller parted ways after the discovery, Ulam returning to his world of pure science, and Teller becoming increasingly belligerent and disliked by his fellow scientists, and pushing for new and "better" nuclear weapons, thus becoming what Richard Rhodes calls the "Richard Nixon of American science". Till the end of his life in 2004 at the age of 95, he gave hawkish and wrong advice to Presidents (famously about "Star Wars" to Ronald Reagan) and believed that he was doing the right thing in advancing peace by building more hydrogen bombs.
During his professional career, Ulam spent time at the Universities of Wisconsin, UCLA, and Boulder. His wife, Francoise, was always a loving support as well as an admirer of him. She remembers one defining moment from their lives, when she found her husband staring out the window after he had had the idea for a successful hydrogen bomb. "I have just discovered the idea that will change history", he presciently said.
Ulam died in 1984. An astonishingly versatile scientist, he had been equally at home with the most abstruse reaches of set theory and with the details of thermonuclear fusion. His memoirs, Adventures of a Mathematician, paints a fascinating and delightful portrait of the golden age of physics and mathematics, as well as the dawn of the nuclear age. In this book, we get to hear anecdotes about famous mathematicians and physicists, many of whom were good friends of Ulam.
Ulam once said:
"Great scientists see analogies between theorems or theories. The very best ones see analogies between analogies"Indeed. And Stan Ulam could very well put himself into the second category, although his modest nature would have not made him do so.
Ulam was born in Poland and grew up in a romantic time in the 20s and 30s, when great discoveries in mathematics and physics were being made in small, enchanting roadside cafes by small groups of people working intensely together. One of those, the Scottish Cafe in Lwow, Poland, was a focal point for meeting of great minds, the best pure mathematicians in Europe. Equations used to be scribbled on tables there, and the waiters were told never to erase them. Marathon sessions used to be common, fueled by black coffee, and interrupted only by occasional meals and trips to the bathroom; one non-stop session lasted 17 hours. The mathematician Rota said this about Ulam's fascinating mind:
"Ulam's mind is a repository of thousands of stories, tales, jokes, epigrams, remarks, puzzles, tounge-twisters, footnotes, conclusions, slogans, formulas, diagrams, quotations, limericks, summaries, quips, epitaphs, and headlines. In the course of a normal conversation he simply pulls out of his mind the fifty-odd relevant items, and presents them in linear succession. A second-order memory prevents him from repeating himself too often before the same public."Ulam was invited to visit the US as a lecturer several times during the 1930s by his fellow famous emigre from Europe, and admittedly the smartest man of his generation; John Von Neumann. Within a short time, the romantic days were at a tragic end. Ulam held out in Poland much longer than many other brilliant European scientists and mathematicians, and in 1939, on the eve of World War 2, escaped to America with his brother Adam. The rest of the Ulam family perished in the Holocaust.
After coming to the US, Ulam was secretly invited to join the Manhattan Project in Los Alamos, where he was known to be a problem solver and jovial team worker. In Los Alamos, he tried to recreate the idyllic atmosphere of his young years in Europe by installing a coffee machine outside his office where scientists could talk shop. You can get to see Ulam in The Day after Trinity. Here is a photo of three prodigies from those days, (From L to R) Ulam, Richard Feynman, and John Von Neumann
While at Los Alamos, Ulam made what was probably the most important contribution of his career- the Monte Carlo method, a way of calculating the result of complex processes through random numbers. This method is now so important and deep-rooted in physics, chemistry, and engineering, that many students have forgotten that somebody invented it. The method is now implemented as a black box in many computer programs, such as those which I use for calculating the structure of organic molecules, and so people tend to sometimes use it without knowing that they are using it.
In 1946, Ulam suffered an attack of encephalitis; he could not remember events after the attack, and after the operation, federal agents asked him questions to make sure that he may not have given away atomic secrets during his loss of recollection. After the operation, Ulam seemed to some to become even more brilliant than he had been before.
However, Ulam probably became best-known to a greater audience through his participation in the development of the hydrogen bomb. After the war, he and fellow scientist Cornelius Everett embarked on a series of tedious calculations to prove that the then accepted and widely touted design of the hydrogen bomb would not work. This was a significant result, as President Harry Truman had been earlier prodded to announce a crash effort to develop the bomb based on this design. WIthin a short time however, Ulam came to the essential breakthrough that encouraged the infamous Edward Teller to develop the most widely used design of the h-bomb. The breakthrough involved separating the fission and fusion parts of the weapons, and using compression from the fission bomb to activate the fusion bomb. After this design was invented, everybody assumed that the Soviets were doing it too, and the program was purused with vigour. Every country afterwards that developed thermonuclear weapons has used this so-called "Teller-Ulam" design or a variant of it.
The imperious Teller essentially took much of the credit for the invention, and later tried to expunge Ulam's name from that part of history. Hans Bethe liked to joke that Ulam was really the "father of the h-bomb" while Teller was the mother since he carried the baby for so long. Ulam for his own part, an unassuming and docile man, stayed away from these disputes, when he rightly could have done more for asserting his claim to fame. Ulam and Teller parted ways after the discovery, Ulam returning to his world of pure science, and Teller becoming increasingly belligerent and disliked by his fellow scientists, and pushing for new and "better" nuclear weapons, thus becoming what Richard Rhodes calls the "Richard Nixon of American science". Till the end of his life in 2004 at the age of 95, he gave hawkish and wrong advice to Presidents (famously about "Star Wars" to Ronald Reagan) and believed that he was doing the right thing in advancing peace by building more hydrogen bombs.
During his professional career, Ulam spent time at the Universities of Wisconsin, UCLA, and Boulder. His wife, Francoise, was always a loving support as well as an admirer of him. She remembers one defining moment from their lives, when she found her husband staring out the window after he had had the idea for a successful hydrogen bomb. "I have just discovered the idea that will change history", he presciently said.
Ulam died in 1984. An astonishingly versatile scientist, he had been equally at home with the most abstruse reaches of set theory and with the details of thermonuclear fusion. His memoirs, Adventures of a Mathematician, paints a fascinating and delightful portrait of the golden age of physics and mathematics, as well as the dawn of the nuclear age. In this book, we get to hear anecdotes about famous mathematicians and physicists, many of whom were good friends of Ulam.
Ulam once said:
"It is still an unending source of surprise for me how a few scribbles on a blackboard or on a piece of paper can change the course of human affairs."Ulam was certainly one of the select few who scribbled.
How not to design a fly killer
Raid "Earth Options" Flying Insect Killer, the supposedly environment-friendly fly spray, is admittedly the worst designed fly killer I have come across until now. I doubt if even the manufacturers themselves knew what composition and materials they put in, and even if they did they don't seem to have actually tested it. For one thing, I don't know if it's because it's supposed to be benign, but its sheer potency is just lousy. You have to spray it directly on the fly, and more often than not the little critter ends up flying around before it suffers a direct hit, so that you mostly end up spraying everywhere else except on it. Even when it is hit, it usually struts around for a few random centimeters before finally falling dead, thus parading microscopic globs of the chemical all over the place. And in some death defying instances, I have even seen flies getting up, dusting themselves off as if nothing happened, and resuming their flying antics.
But the most annoying thing about Raid Earth Options is their aerosol composition, which is extremely poorly designed. The stuff does not perform even its basic function, to get finely aerosolized. I don't what exactly was circulating in the bloodstream of the chemist/engineer who designed it. When you spray the stuff, the particle size it produces is quite large, and so the droplets quickly drop like a stone on whatever surface is below. Because of this problem, not only does it not hang around long enough in the fly's flying space, but one can never use it on tubelights, where flies usually sit, because usually the tubelights are right above your desk and everything on it. The first few times I used it, I had to discard some papers on my desk, clean up the whole surface, and yes, throw away a box of cookies that was actually sitting quite far from where I sprayed the fly killer. I don't think environment-friendly means you can use it as hot sauce for your fried rice.
This problem dictates that to avoid a thin and pretty long-lasting coating on everything in my room, I always lure the fly into a bathroom by turning off all lights except the one there, and then turn the whole bathroom atmosphere into a Raid fest. And don't even think of using it anywhere in your kitchen. Plus, the smell is not exactly enticing, for humans and flies. Dismal. Others seem to agree.
S.C. Johnson and Co., for all those heartwarming commercials that portray three generations of dedicated product manufacturers, shame on you for selling us Raid Earth Options. I do like your Ziploc and Saran Wrap.
Trans-biotin?
Questiion for all the synthetics out there: Does anyone know how common, if at all, is trans-biotin, where the two five-membered rings are fused in a trans manner? If not, how easy/hard is it to make it?
New tagline for SBDD
I have come up with a new tagline for structure based drug design:
For instance, you may think, "Hey, that group seems to hydrogen bond with an NH hydrogen; let me make it more electronegative by putting a nitro group somewhere close to it. Oops! That changed the binging mode completely. Tough luck".
Or "Hmm...it seems that this part of the molecule that forms all these hydrogen bonds is similar to that other molecule in that other protein-ligand complex which shows swashbuckling picomolar activity. Why don't I modify this part of the molecule to resemble the other molecule then?...Oops! Changed the entire binding mode again."
And did I mention...the tagline actually should be "Semi-rational or irrational in foresight, almost always irrational and sometimes rational in hindsight"
And all this is only at the molecular level; I don't even have to get started on how small changes can play havoc with things like solubility, pharmakokinetics and bioavailability, and of course, the notorious tox. Chemists are long familiar with what the addition of a single methyl group can do to binding and activity. At the same time, it's curious how there in fact are so many inhibitors binding to a certain class of proteins that may differ radically in other parts, yet have a highly conserved set of atoms which consistently bind to the same part of the protein. Almost miraculously, all those changes in the other parts don't seem to affect the way those few atoms bind to the protein; the best example that comes to my mind is that almost ubiquitous set of 'hinge binding' atoms in protein kinase inhibitors that mimics the ATP motif. Of course, this makes them wildly non-selective because almost no kinase is 'unhinged', but often puts you at a good starting point in terms of potency.
The fact, we still have miles to go in understanding the subtleties of protein-ligand interaction. But we have also made a mighty fine start in understanding, among other things, subtle differences in Van der Waals interactions, desolvation and entropic penalties, bioisosterism (or the lack thereof), and most recently, the role of water in ligand binding.
It's a good day to be alive sir.
"Semi-rational in foresight, rational in hindsight"And in fact I think that could apply to many aspects of designing drugs.
For instance, you may think, "Hey, that group seems to hydrogen bond with an NH hydrogen; let me make it more electronegative by putting a nitro group somewhere close to it. Oops! That changed the binging mode completely. Tough luck".
Or "Hmm...it seems that this part of the molecule that forms all these hydrogen bonds is similar to that other molecule in that other protein-ligand complex which shows swashbuckling picomolar activity. Why don't I modify this part of the molecule to resemble the other molecule then?...Oops! Changed the entire binding mode again."
And did I mention...the tagline actually should be "Semi-rational or irrational in foresight, almost always irrational and sometimes rational in hindsight"
And all this is only at the molecular level; I don't even have to get started on how small changes can play havoc with things like solubility, pharmakokinetics and bioavailability, and of course, the notorious tox. Chemists are long familiar with what the addition of a single methyl group can do to binding and activity. At the same time, it's curious how there in fact are so many inhibitors binding to a certain class of proteins that may differ radically in other parts, yet have a highly conserved set of atoms which consistently bind to the same part of the protein. Almost miraculously, all those changes in the other parts don't seem to affect the way those few atoms bind to the protein; the best example that comes to my mind is that almost ubiquitous set of 'hinge binding' atoms in protein kinase inhibitors that mimics the ATP motif. Of course, this makes them wildly non-selective because almost no kinase is 'unhinged', but often puts you at a good starting point in terms of potency.
The fact, we still have miles to go in understanding the subtleties of protein-ligand interaction. But we have also made a mighty fine start in understanding, among other things, subtle differences in Van der Waals interactions, desolvation and entropic penalties, bioisosterism (or the lack thereof), and most recently, the role of water in ligand binding.
It's a good day to be alive sir.
R.I.P Frank
Frank Westheimer, rest in peace. I will never forget your Why Nature Chose Phosphates, which was brilliant. Rest assured, you will be more than a footnote to a footnote in the history of chemistry.
Questions for the kinase biologists
I am working on a kinase inhibitor design project and I realised that there are some key questions that we need to get answered from the biologists before we can rationalize the selectivity of various kinase inhibitors for a given binding site. I also realised that these questions need to be answered for many other kinds of protein-inhibitor interactions.
1. Whenever we get different IC50 data for two inhibitors, we immediately try to look at binding interactions that may be different for the two moelcules to rationalize this observation. But as I have alluded before, it's not the IC50 but the Ki that's really to do with different binding interactions. The Ki and IC50 are related by an equation that includes both the Km value of ATP and the concentration of ATP in the two experiments, or in general, these two parameters for the natural binding substrate for the protein. Only if these two are the same for both inhibitor experiments is the IC50=Ki. So make sure you confirm this. Otherwise, extrapolate and calculate the new IC50s based on identical values for these parameters. Then rationalize the IC50s based on binding interactions.
2. For many kinases, three events are absolutely essential for activation:
a. Phosphorylation of one Ser, Thr or Tyr residue,
b. Binding of ATP (duh), and
c. Dephosphorylation of another Ser, Thr or Tyr residue.
Think of it like a logic gate. IF the answers to all a. b. and c. are YES, THEN the kinase will be activated and proceed to perform its function. (I got this from Alberts et al.'s Molecular Biology of the Cell)
In the assays that are run, it is important to know (and not very easy to always determine as I have been told) whether the necessary residue is phosphorylated or not. For one thing, inclusion of this knowledge in your docking and modeling can naturally make a big difference. And secondly, depending on the state of phosphorylation, you can think of different modes of inhibition for your inhibitor (eg. ATP blocking + substrate blocking).
As usual, it's important to know what the biologists are doing. They don't know the nuances of modeling/crystallography and you don't know the nuances of their assays. But it's important for both camps to think of questions which the other camp should answer that will affect their own work.
1. Whenever we get different IC50 data for two inhibitors, we immediately try to look at binding interactions that may be different for the two moelcules to rationalize this observation. But as I have alluded before, it's not the IC50 but the Ki that's really to do with different binding interactions. The Ki and IC50 are related by an equation that includes both the Km value of ATP and the concentration of ATP in the two experiments, or in general, these two parameters for the natural binding substrate for the protein. Only if these two are the same for both inhibitor experiments is the IC50=Ki. So make sure you confirm this. Otherwise, extrapolate and calculate the new IC50s based on identical values for these parameters. Then rationalize the IC50s based on binding interactions.
2. For many kinases, three events are absolutely essential for activation:
a. Phosphorylation of one Ser, Thr or Tyr residue,
b. Binding of ATP (duh), and
c. Dephosphorylation of another Ser, Thr or Tyr residue.
Think of it like a logic gate. IF the answers to all a. b. and c. are YES, THEN the kinase will be activated and proceed to perform its function. (I got this from Alberts et al.'s Molecular Biology of the Cell)
In the assays that are run, it is important to know (and not very easy to always determine as I have been told) whether the necessary residue is phosphorylated or not. For one thing, inclusion of this knowledge in your docking and modeling can naturally make a big difference. And secondly, depending on the state of phosphorylation, you can think of different modes of inhibition for your inhibitor (eg. ATP blocking + substrate blocking).
As usual, it's important to know what the biologists are doing. They don't know the nuances of modeling/crystallography and you don't know the nuances of their assays. But it's important for both camps to think of questions which the other camp should answer that will affect their own work.
Some clerihews
Plug in your own into the comments, and I will gladly update the post!
Albert Einstein
Led by a godly sign
Engaged in spacetime-talk
Forgot to wear a sock
Robert Burns Woodward
Once looked skyward
By cogitation alone
Made strychnine from stone
Julius Robert Oppenheimer
Bought a millisecond timer
Before the timer struck one
Had read Tolstoy "just for fun"
Marie Curie
Exalted was she
Glee she was showing
When the beaker started glowing
Ernest Rutherford
Was made a Lord
By throwing many a dart
Straight into the atom's heart
Richard Philips Feynman
Much fun for the layman
When safes he was poking
Surely he was joking
Finally, an already known classic one (from the Oxford Dictionary):
Sir James Dewar
Is better than you are.
None of you asses
Can liquefy gasses!
Update:
Some choice ones from Peter Ellis,
Alfred Nobel
Did very well
By blowing up things of all sizes
Now his ghost atones for it with prizes
Watson and Crick
Make me feel sick
By uncovering the heart of everything
Using little toy balls and bits of string.
...and A Synthetic Environment.
Marie Curie,
Not hard to see,
Was glowing with pride,
And glowed in the night.
Herr Wöhler, Friedrich
He told his friend Liebig:
'Not now, sorry. See ya!
I’m pissing urea.’
Antoine-Laurent de Lavoisier,
Said : ‘Phlogiston theory is not okay,
This phlogiston theory is driving me mad,
I have to disprove it or I’ll lose my head.’
Robert H. Grubbs,
he visited pubs.
One pub let a bell ring,
That ring meant 'we're closing!'.
Albert Einstein
Led by a godly sign
Engaged in spacetime-talk
Forgot to wear a sock
Robert Burns Woodward
Once looked skyward
By cogitation alone
Made strychnine from stone
Julius Robert Oppenheimer
Bought a millisecond timer
Before the timer struck one
Had read Tolstoy "just for fun"
Marie Curie
Exalted was she
Glee she was showing
When the beaker started glowing
Ernest Rutherford
Was made a Lord
By throwing many a dart
Straight into the atom's heart
Richard Philips Feynman
Much fun for the layman
When safes he was poking
Surely he was joking
Finally, an already known classic one (from the Oxford Dictionary):
Sir James Dewar
Is better than you are.
None of you asses
Can liquefy gasses!
Update:
Some choice ones from Peter Ellis,
Alfred Nobel
Did very well
By blowing up things of all sizes
Now his ghost atones for it with prizes
Watson and Crick
Make me feel sick
By uncovering the heart of everything
Using little toy balls and bits of string.
...and A Synthetic Environment.
Marie Curie,
Not hard to see,
Was glowing with pride,
And glowed in the night.
Herr Wöhler, Friedrich
He told his friend Liebig:
'Not now, sorry. See ya!
I’m pissing urea.’
Antoine-Laurent de Lavoisier,
Said : ‘Phlogiston theory is not okay,
This phlogiston theory is driving me mad,
I have to disprove it or I’ll lose my head.’
Robert H. Grubbs,
he visited pubs.
One pub let a bell ring,
That ring meant 'we're closing!'.
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