[ccp4bb] into the looking glass
Dear CCP4BB, I think it prudent at this point for me to announce what could be a very old, but serious error in the fundamental mathematics of crystallography. To be brief, I have uncovered evidence that the hand of the micro-world is actually the opposite of what we have believed since Bijvoet's classic paper in 1951. Those of you who know me know that I have been trying to lay down the whole of x-ray diffraction into a single program. This is harder than it sounds. We all know what anomalous scattering is, but a detailed description of the math behind translating this dynamical theory effect all the way to the intensity of a particular detector pixel is hard to find all in one place. Most references in the literature about how anomalous scattering is connected to absolute configuration point to the classic Nature paper: Bijvoet et. al. (1951). Unfortunately, since this is a Nature paper, it is too short to describe the math in detail. For the calculations, the reader is referred to another paper by Bijvoet in the Proc. Roy. Acad. Amsterdam v52, 313 (1949). Essentially, the only new information in Bijvoet et. al. (1951) is the assertion that Emil Fischer got it right in his initial (arbitrary) assignment of the R and S reference compounds for the absolute configuration of molecules. I decided to follow this paper trail. The PRAA document was hard to come by and, to my disappointment, again referenced the real calculation to another work. Eventually, however, all roads lead back to R. W. James (1946). This is the definitive textbook on scattering theory (originally edited by Sir Lawrence Bragg himself). It is extremely useful, and I highly recommend that anyone who wants to really understand scattering should read it. However, even this wonderful text does not go through the full quantum-mechanical derivation of scattering, but rather rests on J. J. Thompson's original classical treatment. There is nothing wrong with this because the the exact value of the phase lag of the scattering event does not effect anything as long as the phase lag from all the atoms is the same. The only time it does become important is anomalous scattering. Even so, changing the sign of the phase lag will have no effect on any of the anomalous scattering equations as long as all the anomalous contributions have the same sign. The only time the sign of the phase lag is important is in the assignment of absolute configuration. Unfortunately, a full quantum mechanical treatment of the scattering process DOES produce a phase lag with the opposite sign of the classical treatment. This is not the only example of this sort of thing cropping up. One you can find in any quantum text book is the treatment of tilting a quantum-mechanical spin (such as an electron). It was shown by Heisenberg that a tilt of 360 degrees actually only turns an electron upside-down. You have to tilt it by 720 degrees to restore the initial state, or get it right-side-up again. This is very counterintuitive, but true, and unfortunately a similar treatment of scattering results in a phase lag of +270 degrees to restore the electron after the scattering event, not +90 degrees as was derived classically. To be brief, there is a sign error. Perhaps the reason why noone caught this until now is not just that the quantum calculations are a pain, but that it was very tempting to accept that the large body of literature following Fischer's convention would not have to be corrected by inverting the hand of every chiral center described up to that time. Unfortunately, we now have an even larger body of literature (including the PDB) that must now be corrected. It is an under-appreciated fact in chemistry that anomalous scattering is arguably the only direct evidence we have about the hand of the micro-world. There are other lines of evidence, such as the morphology of macroscopic crystals and some recent STEM-type microscope observations of DNA. However, as someone with a lot of experience in motor control I don't mind telling you how easy it is to make a sign error in the direction of an axis. This is especially easy when the range of motion of the axis is too small to see by eye. You end up just swapping wires and flipping bits in the axis definitions until you get it right. The right configuration (we have all assumed) is the one asserted in Bijvoet et. al. (1951). Apparently, the STEM observations fell prey to such a mistake. But can you blame them? Inverting the hand of the world is going to be very hard for a lot of people to accept. Indeed, if anyone can find an error in my math, please tell me! I would really like to be wrong about this. -James Holton MAD Scientist
Re: [ccp4bb] into the looking glass
Have to learn crystallography again.. and now along with quantum mechanics! worried Anthony Dear CCP4BB, I think it prudent at this point for me to announce what could be a very old, but serious error in the fundamental mathematics of crystallography. To be brief, I have uncovered evidence that the hand of the micro-world is actually the opposite of what we have believed since Bijvoet's classic paper in 1951. Those of you who know me know that I have been trying to lay down the whole of x-ray diffraction into a single program. This is harder than it sounds. We all know what anomalous scattering is, but a detailed description of the math behind translating this dynamical theory effect all the way to the intensity of a particular detector pixel is hard to find all in one place. Most references in the literature about how anomalous scattering is connected to absolute configuration point to the classic Nature paper: Bijvoet et. al. (1951). Unfortunately, since this is a Nature paper, it is too short to describe the math in detail. For the calculations, the reader is referred to another paper by Bijvoet in the Proc. Roy. Acad. Amsterdam v52, 313 (1949). Essentially, the only new information in Bijvoet et. al. (1951) is the assertion that Emil Fischer got it right in his initial (arbitrary) assignment of the R and S reference compounds for the absolute configuration of molecules. I decided to follow this paper trail. The PRAA document was hard to come by and, to my disappointment, again referenced the real calculation to another work. Eventually, however, all roads lead back to R. W. James (1946). This is the definitive textbook on scattering theory (originally edited by Sir Lawrence Bragg himself). It is extremely useful, and I highly recommend that anyone who wants to really understand scattering should read it. However, even this wonderful text does not go through the full quantum-mechanical derivation of scattering, but rather rests on J. J. Thompson's original classical treatment. There is nothing wrong with this because the the exact value of the phase lag of the scattering event does not effect anything as long as the phase lag from all the atoms is the same. The only time it does become important is anomalous scattering. Even so, changing the sign of the phase lag will have no effect on any of the anomalous scattering equations as long as all the anomalous contributions have the same sign. The only time the sign of the phase lag is important is in the assignment of absolute configuration. Unfortunately, a full quantum mechanical treatment of the scattering process DOES produce a phase lag with the opposite sign of the classical treatment. This is not the only example of this sort of thing cropping up. One you can find in any quantum text book is the treatment of tilting a quantum-mechanical spin (such as an electron). It was shown by Heisenberg that a tilt of 360 degrees actually only turns an electron upside-down. You have to tilt it by 720 degrees to restore the initial state, or get it right-side-up again. This is very counterintuitive, but true, and unfortunately a similar treatment of scattering results in a phase lag of +270 degrees to restore the electron after the scattering event, not +90 degrees as was derived classically. To be brief, there is a sign error. Perhaps the reason why noone caught this until now is not just that the quantum calculations are a pain, but that it was very tempting to accept that the large body of literature following Fischer's convention would not have to be corrected by inverting the hand of every chiral center described up to that time. Unfortunately, we now have an even larger body of literature (including the PDB) that must now be corrected. It is an under-appreciated fact in chemistry that anomalous scattering is arguably the only direct evidence we have about the hand of the micro-world. There are other lines of evidence, such as the morphology of macroscopic crystals and some recent STEM-type microscope observations of DNA. However, as someone with a lot of experience in motor control I don't mind telling you how easy it is to make a sign error in the direction of an axis. This is especially easy when the range of motion of the axis is too small to see by eye. You end up just swapping wires and flipping bits in the axis definitions until you get it right. The right configuration (we have all assumed) is the one asserted in Bijvoet et. al. (1951). Apparently, the STEM observations fell prey to such a mistake. But can you blame them? Inverting the hand of the world is going to be very hard for a lot of people to accept. Indeed, if anyone can find an error in my math, please tell me! I would really like to be wrong about this. -James Holton MAD Scientist
Re: [ccp4bb] into the looking glass
Dear James! Initially I was shocked by the profound implications of your discovery! I immmediately phoned my good friend, Sen. John McCain, to discuss the issue. As you know, Sen. McCain was an aspiring physicist back in the 1920s, when he was in his forties. He pointed me to a little known note (*) by Planck, Slater and Oppenheimer that showed that Heisenberg's assertion is only true under very special spatio-temporal circumstances. In layman's terms, it means that the effect operates only on Earth, and only on a particular day of the year (usually the 91st day, but occasionally the 92nd - I'll spare you the math). So, provided that we don't study, use or publish any structures on those exact space-time coordinates, I think we can safely continue with the established practice. Nevertheless, I will use all the leverage I have at the Royal Swedish Academy of Sciences to get the Nobel Committee for Physics to give your discovery in quantum-crystallography the recognition that it deserves! You are the living proof that not all Physics Nobel Laureates need to be brilliant youngsters! With warm wishes, --Gerard (*) In the little-known journal: Ann. Phys. Relativ. Instrum. Lab., 1. ** Gerard J. Kleywegt [Research Fellow of the Royal Swedish Academy of Sciences] Dept. of Cell Molecular Biology University of Uppsala Biomedical Centre Box 596 SE-751 24 Uppsala SWEDEN http://xray.bmc.uu.se/gerard/ mailto:[EMAIL PROTECTED] ** The opinions in this message are fictional. Any similarity to actual opinions, living or dead, is purely coincidental. **
Re: [ccp4bb] into the looking glass
I lost track. What's the date today? On Tue, 1 Apr 2008, James Holton wrote: Dear CCP4BB, I think it prudent at this point for me to announce what could be a very old, but serious error in the fundamental mathematics of crystallography. To be brief, I have uncovered evidence that the hand of the micro-world is actually the opposite of what we have believed since Bijvoet's classic paper in 1951. Those of you who know me know that I have been trying to lay down the whole of x-ray diffraction into a single program. This is harder than it sounds. We all know what anomalous scattering is, but a detailed description of the math behind translating this dynamical theory effect all the way to the intensity of a particular detector pixel is hard to find all in one place. Most references in the literature about how anomalous scattering is connected to absolute configuration point to the classic Nature paper: Bijvoet et. al. (1951). Unfortunately, since this is a Nature paper, it is too short to describe the math in detail. For the calculations, the reader is referred to another paper by Bijvoet in the Proc. Roy. Acad. Amsterdam v52, 313 (1949). Essentially, the only new information in Bijvoet et. al. (1951) is the assertion that Emil Fischer got it right in his initial (arbitrary) assignment of the R and S reference compounds for the absolute configuration of molecules. I decided to follow this paper trail. The PRAA document was hard to come by and, to my disappointment, again referenced the real calculation to another work. Eventually, however, all roads lead back to R. W. James (1946). This is the definitive textbook on scattering theory (originally edited by Sir Lawrence Bragg himself). It is extremely useful, and I highly recommend that anyone who wants to really understand scattering should read it. However, even this wonderful text does not go through the full quantum-mechanical derivation of scattering, but rather rests on J. J. Thompson's original classical treatment. There is nothing wrong with this because the the exact value of the phase lag of the scattering event does not effect anything as long as the phase lag from all the atoms is the same. The only time it does become important is anomalous scattering. Even so, changing the sign of the phase lag will have no effect on any of the anomalous scattering equations as long as all the anomalous contributions have the same sign. The only time the sign of the phase lag is important is in the assignment of absolute configuration. Unfortunately, a full quantum mechanical treatment of the scattering process DOES produce a phase lag with the opposite sign of the classical treatment. This is not the only example of this sort of thing cropping up. One you can find in any quantum text book is the treatment of tilting a quantum-mechanical spin (such as an electron). It was shown by Heisenberg that a tilt of 360 degrees actually only turns an electron upside-down. You have to tilt it by 720 degrees to restore the initial state, or get it right-side-up again. This is very counterintuitive, but true, and unfortunately a similar treatment of scattering results in a phase lag of +270 degrees to restore the electron after the scattering event, not +90 degrees as was derived classically. To be brief, there is a sign error. Perhaps the reason why noone caught this until now is not just that the quantum calculations are a pain, but that it was very tempting to accept that the large body of literature following Fischer's convention would not have to be corrected by inverting the hand of every chiral center described up to that time. Unfortunately, we now have an even larger body of literature (including the PDB) that must now be corrected. It is an under-appreciated fact in chemistry that anomalous scattering is arguably the only direct evidence we have about the hand of the micro-world. There are other lines of evidence, such as the morphology of macroscopic crystals and some recent STEM-type microscope observations of DNA. However, as someone with a lot of experience in motor control I don't mind telling you how easy it is to make a sign error in the direction of an axis. This is especially easy when the range of motion of the axis is too small to see by eye. You end up just swapping wires and flipping bits in the axis definitions until you get it right. The right configuration (we have all assumed) is the one asserted in Bijvoet et. al. (1951). Apparently, the STEM observations fell prey to such a mistake. But can you blame them? Inverting the hand of the world is going to be very hard for a lot of people to accept. Indeed, if anyone can find an error in my math, please tell me! I would really like to be wrong about this. -James Holton MAD Scientist -- = Robert M. Sweet
Re: [ccp4bb] into the looking glass
James: I have been unable to find any logical flaw in your great chain of reasoning, in spite of the several minutes I spent contemplating it over a mug of lukewarm tea. Given that you are doubtless also correct that, Inverting the 'hand of the world' is going to be very hard for a lot of people to accept, I propose a radical divergence from the entire hand concept, a sort of starting over from scratch methodology, to avoid (as much as possible) any further confusion. Given that Google (in particular) has shown great interest in digitizing all forms of recorded media, I suggest a simple search+replace algorithm, locating all crystallography papers of the past 60 years in the great Googlebase (by the simple expedient of assuming that anything with the word crystallography in the title qualifies; the Google people may wish to participate in this effort), and then replacing any instances of the string right hand with the string left foot. I believe the concept of footedness will, in this way, catch on quickly, and readily address all of the problems brought forth by your research. I would hesitate to refer to this as my left footedness concept, but one is tempted... -- Steve Lane System, Network and Security Administrator Doudna Lab Biomolecular Structure and Mechanism Group UC Berkeley On Tue, Apr 01, 2008 at 10:59:34AM -0700, James Holton wrote: Dear CCP4BB, I think it prudent at this point for me to announce what could be a very old, but serious error in the fundamental mathematics of crystallography. To be brief, I have uncovered evidence that the hand of the micro-world is actually the opposite of what we have believed since Bijvoet's classic paper in 1951. Those of you who know me know that I have been trying to lay down the whole of x-ray diffraction into a single program. This is harder than it sounds. We all know what anomalous scattering is, but a detailed description of the math behind translating this dynamical theory effect all the way to the intensity of a particular detector pixel is hard to find all in one place. Most references in the literature about how anomalous scattering is connected to absolute configuration point to the classic Nature paper: Bijvoet et. al. (1951). Unfortunately, since this is a Nature paper, it is too short to describe the math in detail. For the calculations, the reader is referred to another paper by Bijvoet in the Proc. Roy. Acad. Amsterdam v52, 313 (1949). Essentially, the only new information in Bijvoet et. al. (1951) is the assertion that Emil Fischer got it right in his initial (arbitrary) assignment of the R and S reference compounds for the absolute configuration of molecules. I decided to follow this paper trail. The PRAA document was hard to come by and, to my disappointment, again referenced the real calculation to another work. Eventually, however, all roads lead back to R. W. James (1946). This is the definitive textbook on scattering theory (originally edited by Sir Lawrence Bragg himself). It is extremely useful, and I highly recommend that anyone who wants to really understand scattering should read it. However, even this wonderful text does not go through the full quantum-mechanical derivation of scattering, but rather rests on J. J. Thompson's original classical treatment. There is nothing wrong with this because the the exact value of the phase lag of the scattering event does not effect anything as long as the phase lag from all the atoms is the same. The only time it does become important is anomalous scattering. Even so, changing the sign of the phase lag will have no effect on any of the anomalous scattering equations as long as all the anomalous contributions have the same sign. The only time the sign of the phase lag is important is in the assignment of absolute configuration. Unfortunately, a full quantum mechanical treatment of the scattering process DOES produce a phase lag with the opposite sign of the classical treatment. This is not the only example of this sort of thing cropping up. One you can find in any quantum text book is the treatment of tilting a quantum-mechanical spin (such as an electron). It was shown by Heisenberg that a tilt of 360 degrees actually only turns an electron upside-down. You have to tilt it by 720 degrees to restore the initial state, or get it right-side-up again. This is very counterintuitive, but true, and unfortunately a similar treatment of scattering results in a phase lag of +270 degrees to restore the electron after the scattering event, not +90 degrees as was derived classically. To be brief, there is a sign error. Perhaps the reason why noone caught this until now is not just that the quantum calculations are a pain, but that it was very tempting to accept that the large body of literature following Fischer's convention would not have to be
[ccp4bb] advice regarding computer hardware purchase
Hello everyone, I have not done much crystallography in the past five years but I'm trying to get back into it now because we stumbled upon a very interesting enzyme. It seems a lot has changed in the computer hardware world. I was trained on an SGI back in graduate school. What kind of hardware should I purchase to run all the popular crystallography software? Also, which operating system will give me the least headache? We are basically starting from scratch. Our department has a new Bruker machine and an older Rigaku we can use. Any advice you may have will be greatly appreciated. Thanks in advance for your comments. Chu-Young Kim
Re: [ccp4bb] into the looking glass
James must be too fast - he better be to follow the 93,000 (or is it more?) csh lines of code in Elves in the speed I recall he does. So, most likely he lost less time writing it than us reading it: its a cunning plot, he is wasting our time not his. A. On 1 Apr 2008, at 21:54, So Iwata wrote: Great job. But don't you have any better things to do (tm) ? s. On 1 Apr 2008, at 18:59, James Holton wrote: Dear CCP4BB, I think it prudent at this point for me to announce what could be a very old, but serious error in the fundamental mathematics of crystallography. To be brief, I have uncovered evidence that the hand of the micro-world is actually the opposite of what we have believed since Bijvoet's classic paper in 1951. Those of you who know me know that I have been trying to lay down the whole of x-ray diffraction into a single program. This is harder than it sounds. We all know what anomalous scattering is, but a detailed description of the math behind translating this dynamical theory effect all the way to the intensity of a particular detector pixel is hard to find all in one place. Most references in the literature about how anomalous scattering is connected to absolute configuration point to the classic Nature paper: Bijvoet et. al. (1951). Unfortunately, since this is a Nature paper, it is too short to describe the math in detail. For the calculations, the reader is referred to another paper by Bijvoet in the Proc. Roy. Acad. Amsterdam v52, 313 (1949). Essentially, the only new information in Bijvoet et. al. (1951) is the assertion that Emil Fischer got it right in his initial (arbitrary) assignment of the R and S reference compounds for the absolute configuration of molecules. I decided to follow this paper trail. The PRAA document was hard to come by and, to my disappointment, again referenced the real calculation to another work. Eventually, however, all roads lead back to R. W. James (1946). This is the definitive textbook on scattering theory (originally edited by Sir Lawrence Bragg himself). It is extremely useful, and I highly recommend that anyone who wants to really understand scattering should read it. However, even this wonderful text does not go through the full quantum-mechanical derivation of scattering, but rather rests on J. J. Thompson's original classical treatment. There is nothing wrong with this because the the exact value of the phase lag of the scattering event does not effect anything as long as the phase lag from all the atoms is the same. The only time it does become important is anomalous scattering. Even so, changing the sign of the phase lag will have no effect on any of the anomalous scattering equations as long as all the anomalous contributions have the same sign. The only time the sign of the phase lag is important is in the assignment of absolute configuration. Unfortunately, a full quantum mechanical treatment of the scattering process DOES produce a phase lag with the opposite sign of the classical treatment. This is not the only example of this sort of thing cropping up. One you can find in any quantum text book is the treatment of tilting a quantum- mechanical spin (such as an electron). It was shown by Heisenberg that a tilt of 360 degrees actually only turns an electron upside-down. You have to tilt it by 720 degrees to restore the initial state, or get it right-side-up again. This is very counterintuitive, but true, and unfortunately a similar treatment of scattering results in a phase lag of +270 degrees to restore the electron after the scattering event, not +90 degrees as was derived classically. To be brief, there is a sign error. Perhaps the reason why noone caught this until now is not just that the quantum calculations are a pain, but that it was very tempting to accept that the large body of literature following Fischer's convention would not have to be corrected by inverting the hand of every chiral center described up to that time. Unfortunately, we now have an even larger body of literature (including the PDB) that must now be corrected. It is an under-appreciated fact in chemistry that anomalous scattering is arguably the only direct evidence we have about the hand of the micro-world. There are other lines of evidence, such as the morphology of macroscopic crystals and some recent STEM-type microscope observations of DNA. However, as someone with a lot of experience in motor control I don't mind telling you how easy it is to make a sign error in the direction of an axis. This is especially easy when the range of motion of the axis is too small to see by eye. You end up just swapping wires and flipping bits in the axis definitions until you get it right. The right configuration (we have all assumed) is the one asserted in Bijvoet et. al. (1951). Apparently,
Re: [ccp4bb] advice regarding computer hardware purchase
Hi Chu-Young: I would recommend either a PC running Ubuntu Linux (my personal favorite distribution -- they are all more or less the same thing) or else Apple Mac OS X, depending upon your other needs, budget, etc. I've got a lot of propaganda for OS X here: http://xanana.ucsc.edu/xtal and a little bit for Ubuntu Linux here: http://xanana.ucsc.edu/linux/debian_linux.html Welcome back. Bill William G. Scott Contact info: http://chemistry.ucsc.edu/~wgscott/ On Apr 1, 2008, at 1:04 PM, Chu-Young Kim wrote: Hello everyone, I have not done much crystallography in the past five years but I'm trying to get back into it now because we stumbled upon a very interesting enzyme. It seems a lot has changed in the computer hardware world. I was trained on an SGI back in graduate school. What kind of hardware should I purchase to run all the popular crystallography software? Also, which operating system will give me the least headache? We are basically starting from scratch. Our department has a new Bruker machine and an older Rigaku we can use. Any advice you may have will be greatly appreciated. Thanks in advance for your comments. Chu-Young Kim
[ccp4bb] TLS, B factors, phenix and refmac
Hi - Prompted by the recent discussions on B values, TLS refinement and differences between Phenix and refmac, we looked into these matters in more detail. We found that the crux of the problem lies in the fact that TLS and B value refinements are usually decoupled. We have developed a formalism that rolls both TLS and B value refinement into one. Phenix and refmac were modified to carry out the calculations, and the outputs from both programs were made compatible to allow proper comparison of the results. We found that the stability of the refinements is now vastly improved. More importantly, however, due to the reduced number of parameters, these calculations can be carried out to resolutions of 7 Å with meaningful representations of indiviual, anisotropic atomic displacement parameters. This low-resolution limit required reformulating the calculation of Wilson B values, but that is only a minor aspect of our treatment that can be neglected. The new, combined procedure for the simultaneous refinement of TLS/B is called 'TBS' refinement, reflecting all required components: Translation, Bibation, Screw. Interestingly, the ‘T’ component is fairly insensitive to input parameters, whereas the overall quality of the refinement is greatly dependent on the ‘B’ component. The more emphasis is put on ‘B’, the more convincing the results. There is a limit, though. At very high levels of ‘B’, the so-called ‘bibacity limit’, the refinement becomes very unstable, leading to inversion in severe cases. Seasoned crystallographers familiar with the concepts can successfully push the procedure to quite high 'B limits', whereas less experienced practitioners should follow the protocols very carefully. Please contact us for any details. Best - MM Mischa Machius, PhD Associate Professor UT Southwestern Medical Center at Dallas 5323 Harry Hines Blvd.; ND10.214A Dallas, TX 75390-8816; U.S.A. Tel: +1 214 645 6381 Fax: +1 214 645 6353
Re: [ccp4bb] into the looking glass
Great job. But don't you have any better things to do (tm) ? s. On 1 Apr 2008, at 18:59, James Holton wrote: Dear CCP4BB, I think it prudent at this point for me to announce what could be a very old, but serious error in the fundamental mathematics of crystallography. To be brief, I have uncovered evidence that the hand of the micro-world is actually the opposite of what we have believed since Bijvoet's classic paper in 1951. Those of you who know me know that I have been trying to lay down the whole of x-ray diffraction into a single program. This is harder than it sounds. We all know what anomalous scattering is, but a detailed description of the math behind translating this dynamical theory effect all the way to the intensity of a particular detector pixel is hard to find all in one place. Most references in the literature about how anomalous scattering is connected to absolute configuration point to the classic Nature paper: Bijvoet et. al. (1951). Unfortunately, since this is a Nature paper, it is too short to describe the math in detail. For the calculations, the reader is referred to another paper by Bijvoet in the Proc. Roy. Acad. Amsterdam v52, 313 (1949). Essentially, the only new information in Bijvoet et. al. (1951) is the assertion that Emil Fischer got it right in his initial (arbitrary) assignment of the R and S reference compounds for the absolute configuration of molecules. I decided to follow this paper trail. The PRAA document was hard to come by and, to my disappointment, again referenced the real calculation to another work. Eventually, however, all roads lead back to R. W. James (1946). This is the definitive textbook on scattering theory (originally edited by Sir Lawrence Bragg himself). It is extremely useful, and I highly recommend that anyone who wants to really understand scattering should read it. However, even this wonderful text does not go through the full quantum-mechanical derivation of scattering, but rather rests on J. J. Thompson's original classical treatment. There is nothing wrong with this because the the exact value of the phase lag of the scattering event does not effect anything as long as the phase lag from all the atoms is the same. The only time it does become important is anomalous scattering. Even so, changing the sign of the phase lag will have no effect on any of the anomalous scattering equations as long as all the anomalous contributions have the same sign. The only time the sign of the phase lag is important is in the assignment of absolute configuration. Unfortunately, a full quantum mechanical treatment of the scattering process DOES produce a phase lag with the opposite sign of the classical treatment. This is not the only example of this sort of thing cropping up. One you can find in any quantum text book is the treatment of tilting a quantum-mechanical spin (such as an electron). It was shown by Heisenberg that a tilt of 360 degrees actually only turns an electron upside-down. You have to tilt it by 720 degrees to restore the initial state, or get it right-side-up again. This is very counterintuitive, but true, and unfortunately a similar treatment of scattering results in a phase lag of +270 degrees to restore the electron after the scattering event, not +90 degrees as was derived classically. To be brief, there is a sign error. Perhaps the reason why noone caught this until now is not just that the quantum calculations are a pain, but that it was very tempting to accept that the large body of literature following Fischer's convention would not have to be corrected by inverting the hand of every chiral center described up to that time. Unfortunately, we now have an even larger body of literature (including the PDB) that must now be corrected. It is an under-appreciated fact in chemistry that anomalous scattering is arguably the only direct evidence we have about the hand of the micro-world. There are other lines of evidence, such as the morphology of macroscopic crystals and some recent STEM-type microscope observations of DNA. However, as someone with a lot of experience in motor control I don't mind telling you how easy it is to make a sign error in the direction of an axis. This is especially easy when the range of motion of the axis is too small to see by eye. You end up just swapping wires and flipping bits in the axis definitions until you get it right. The right configuration (we have all assumed) is the one asserted in Bijvoet et. al. (1951). Apparently, the STEM observations fell prey to such a mistake. But can you blame them? Inverting the hand of the world is going to be very hard for a lot of people to accept. Indeed, if anyone can find an error in my math, please tell me! I would really like to be wrong about this. -James Holton MAD
Re: [ccp4bb] [phenixbb] TLS, B factors, phenix and refmac
I think what you describe below is a bit of re-inventing the wheel (in some sense, not completely). Here is why: phenix.refine has an extremely complex algorithm of refinement ADP. By refining ADP I mean refining of all U=Utls+Ucryst+Uresidual. Briefly: - it does some group iso B refinement to get starting TLS values; - then it simultaneously refines TLS parameters and residual B; - then it extracts TLS components from total B as described in http://www.ccp4.ac.uk/newsletters/newsletter45.pdf; - it monitors to make sure that all parameters are meaningful at all times; - then it repeats the whole process at next macro-cycle. Look TLS related code in phenix.refine for more details. The all details and parameters of the above algorithm were highly optimized using systematic re-refinement of 355 models selected from PDB. This makes ADP refinement (TLS+B+etc) in phenix very stable. See dedicated slide here, for actual results: http://phenix-online.org/download/documentation/cci_apps/phenix_refine_quick_facts.pdf At some point, I re-refined all models in PDB (that have data) using TLS refinement option in phenix.refine. It never crashed or got unstabale. So, I don't think there is anything to improve in terms of stability of TLS refinement in PHENIX. Please let me know if you find a case where this algorithm implemented in phenix.refine fails and I will try to fix it asap. Cheers, Pavel. On 4/1/2008 1:01 PM, Mischa Machius wrote: Hi - Prompted by the recent discussions on B values, TLS refinement and differences between Phenix and refmac, we looked into these matters in more detail. We found that the crux of the problem lies in the fact that TLS and B value refinements are usually decoupled. We have developed a formalism that rolls both TLS and B value refinement into one. Phenix and refmac were modified to carry out the calculations, and the outputs from both programs were made compatible to allow proper comparison of the results. We found that the stability of the refinements is now vastly improved. More importantly, however, due to the reduced number of parameters, these calculations can be carried out to resolutions of 7 Å with meaningful representations of indiviual, anisotropic atomic displacement parameters. This low-resolution limit required reformulating the calculation of Wilson B values, but that is only a minor aspect of our treatment that can be neglected. The new, combined procedure for the simultaneous refinement of TLS/B is called 'TBS' refinement, reflecting all required components: Translation, Bibation, Screw. Interestingly, the ‘T’ component is fairly insensitive to input parameters, whereas the overall quality of the refinement is greatly dependent on the ‘B’ component. The more emphasis is put on ‘B’, the more convincing the results. There is a limit, though. At very high levels of ‘B’, the so-called ‘bibacity limit’, the refinement becomes very unstable, leading to inversion in severe cases. Seasoned crystallographers familiar with the concepts can successfully push the procedure to quite high 'B limits', whereas less experienced practitioners should follow the protocols very carefully. Please contact us for any details. Best - MM Mischa Machius, PhD Associate Professor UT Southwestern Medical Center at Dallas 5323 Harry Hines Blvd.; ND10.214A Dallas, TX 75390-8816; U.S.A. Tel: +1 214 645 6381 Fax: +1 214 645 6353 ___ phenixbb mailing list [EMAIL PROTECTED] http://www.phenix-online.org/mailman/listinfo/phenixbb
[ccp4bb] convenient means to find I/sigma for publications?
Hello all, Silly question, but what is the most convenient means to find the overall I/sigma and the I/sigma for the highest resolution shell in CCP4? At the end of refinement and validation, and after running PROCHECK, I am still using a very convoluted route to obtaining these numbers. Thanks! JMP You rock. That's why Blockbuster's offering you one month of Blockbuster Total Access, No Cost. http://tc.deals.yahoo.com/tc/blockbuster/text5.com
Re: [ccp4bb] into the looking glass
Hey guys, what day is today? I think this was very funny... James Holton [EMAIL PROTECTED] schrieb: Dear CCP4BB, I think it prudent at this point for me to announce what could be a very old, but serious error in the fundamental mathematics of crystallography. To be brief, I have uncovered evidence that the hand of the micro-world is actually the opposite of what we have believed since Bijvoet's classic paper in 1951. Those of you who know me know that I have been trying to lay down the whole of x-ray diffraction into a single program. This is harder than it sounds. We all know what anomalous scattering is, but a detailed description of the math behind translating this dynamical theory effect all the way to the intensity of a particular detector pixel is hard to find all in one place. Most references in the literature about how anomalous scattering is connected to absolute configuration point to the classic Nature paper: Bijvoet et. al. (1951). Unfortunately, since this is a Nature paper, it is too short to describe the math in detail. For the calculations, the reader is referred to another paper by Bijvoet in the Proc. Roy. Acad. Amsterdam v52, 313 (1949). Essentially, the only new information in Bijvoet et. al. (1951) is the assertion that Emil Fischer got it right in his initial (arbitrary) assignment of the R and S reference compounds for the absolute configuration of molecules. I decided to follow this paper trail. The PRAA document was hard to come by and, to my disappointment, again referenced the real calculation to another work. Eventually, however, all roads lead back to R. W. James (1946). This is the definitive textbook on scattering theory (originally edited by Sir Lawrence Bragg himself). It is extremely useful, and I highly recommend that anyone who wants to really understand scattering should read it. However, even this wonderful text does not go through the full quantum-mechanical derivation of scattering, but rather rests on J. J. Thompson's original classical treatment. There is nothing wrong with this because the the exact value of the phase lag of the scattering event does not effect anything as long as the phase lag from all the atoms is the same. The only time it does become important is anomalous scattering. Even so, changing the sign of the phase lag will have no effect on any of the anomalous scattering equations as long as all the anomalous contributions have the same sign. The only time the sign of the phase lag is important is in the assignment of absolute configuration. Unfortunately, a full quantum mechanical treatment of the scattering process DOES produce a phase lag with the opposite sign of the classical treatment. This is not the only example of this sort of thing cropping up. One you can find in any quantum text book is the treatment of tilting a quantum-mechanical spin (such as an electron). It was shown by Heisenberg that a tilt of 360 degrees actually only turns an electron upside-down. You have to tilt it by 720 degrees to restore the initial state, or get it right-side-up again. This is very counterintuitive, but true, and unfortunately a similar treatment of scattering results in a phase lag of +270 degrees to restore the electron after the scattering event, not +90 degrees as was derived classically. To be brief, there is a sign error. Perhaps the reason why noone caught this until now is not just that the quantum calculations are a pain, but that it was very tempting to accept that the large body of literature following Fischer's convention would not have to be corrected by inverting the hand of every chiral center described up to that time. Unfortunately, we now have an even larger body of literature (including the PDB) that must now be corrected. It is an under-appreciated fact in chemistry that anomalous scattering is arguably the only direct evidence we have about the hand of the micro-world. There are other lines of evidence, such as the morphology of macroscopic crystals and some recent STEM-type microscope observations of DNA. However, as someone with a lot of experience in motor control I don't mind telling you how easy it is to make a sign error in the direction of an axis. This is especially easy when the range of motion of the axis is too small to see by eye. You end up just swapping wires and flipping bits in the axis definitions until you get it right. The right configuration (we have all assumed) is the one asserted in Bijvoet et. al. (1951). Apparently, the STEM observations fell prey to such a mistake. But can you blame them? Inverting the hand of the world is going to be very hard for a lot of people to accept. Indeed, if anyone can find an error in my math, please tell me! I would really like to be wrong about this. -James Holton MAD Scientist - E-Mails jetzt auf Ihrem
Re: [ccp4bb] advice regarding computer hardware purchase
Chu-Young Kim wrote: Hello everyone, I have not done much crystallography in the past five years but I'm trying to get back into it now because we stumbled upon a very interesting enzyme. It seems a lot has changed in the computer hardware world. I was trained on an SGI back in graduate school. What kind of hardware should I purchase to run all the popular crystallography software? Also, which operating system will give me the least headache? We are basically starting from scratch. Our department has a new Bruker machine and an older Rigaku we can use. Any advice you may have will be greatly appreciated. Thanks in advance for your comments. Chu-Young Kim Almost any kind of recent PC equipped with a Linux distribution and a discrete graphics card capable of 3D acceleration is a cost-effective solution. You don't need much of a machine to run rings around the most powerful SGIs. I'm running Fedora Core 6 with an bunch of aging Pentium 4 single core CPU workstations equipped with NVidia Quadro 980XGL graphics cards. If you don't need stereo, any lower-end GeForce Nvidia graphics card has plenty of horsepower. The biggest headache with Linux is getting all the hardware to play together nicely, and tracking down dependencies for third-party software. It's not that hard to do, just time-consuming. I transitioned from RedHat 9 to Fedora Core 6 within the last year, and there were a number of little issues that had to be addressed to get everything running just right. Once running, Linux workstations are trouble-free and dependable. You can do a lot in Windows now, but it is slow compared to Linux, scripting is awkward, and not everything is available in Windows versions. If you go with Linux, strongly consider an NVidia graphics card. ATI cards have been more problematic to configure satisfactorily. As always, YMMV. Cheers, -- Roger S. Rowlett Professor Colgate University Presidential Scholar Department of Chemistry Colgate University 13 Oak Drive Hamilton, NY 13346 tel: (315)-228-7245 ofc: (315)-228-7395 fax: (315)-228-7935 email: [EMAIL PROTECTED]
Re: [ccp4bb] advice regarding computer hardware purchase
Chu-Young Kim schrieb: Hello everyone, I have not done much crystallography in the past five years but I'm trying to get back into it now because we stumbled upon a very interesting enzyme. It seems a lot has changed in the computer hardware world. I was trained on an SGI back in graduate school. What kind of hardware should I purchase to run all the popular crystallography software? Also, which operating system will give me the least headache? We are basically starting from scratch. Our department has a new Bruker machine and an older Rigaku we can use. Any advice you may have will be greatly appreciated. Thanks in advance for your comments. Chu-Young Kim Hi, we've just bought 4 Dell Vostro 400 MT for the lab, at a price of about 600,-€ a piece (this includes quadcore Q6600 CPUs, 3GB of memory, a big disk and NVidia 8600 GTS graphics; additionally they need a GB ethernet PCI card for 5-10 €). I've tested the machines - they are very fast concerning CPU, disk and graphics. Like for most new hardware, make sure you switch the SATA adapter to RAID mode (default is IDE mode) in the BIOS before you install Linux. We install CentOS-5 - see http://strucbio.biologie.uni-konstanz.de/ccp4wiki/index.php/CentOS HTH, Kay -- Kay Diederichs http://strucbio.biologie.uni-konstanz.de email: [EMAIL PROTECTED] Tel +49 7531 88 4049 Fax 3183 Fachbereich Biologie, Universität Konstanz, Box M647, D-78457 Konstanz smime.p7s Description: S/MIME Cryptographic Signature
Re: [ccp4bb] into the looking glass
As someone who is currently only able to use my left foot I must say I like your way of thinking, Steve. (I broke my right ankle Mar 5). Still can't walk, but at least I have one leg to stand on... I myself am a left-handed human, and I admit I do find some devious pleasure in this reversal of fortunes. Perhaps it is some deep-seated suppressed anger from my days in kindergarten searching through piles of scissors for those few lefty ones that the oppressive rightist majority tossed into the pile to placate us. Perhaps it is my frustration with chirally prejudiced pointing devices that has led me to hate GUIs so much. Perhaps it was learning the etymology of words like sinister and how us lefties were nearly driven to extinction in the middle ages. Whatever the case, it does now appear that right is not right. So. Ha Ha! Chalk up one for the lefties! One day we will rise up and take back what is leftfully ours! Or maybe I've been watching too much TV. Happy April Fool everyone! -James Holton MAD Scientist Steve Lane wrote: James: I have been unable to find any logical flaw in your great chain of reasoning, in spite of the several minutes I spent contemplating it over a mug of lukewarm tea. Given that you are doubtless also correct that, Inverting the 'hand of the world' is going to be very hard for a lot of people to accept, I propose a radical divergence from the entire hand concept, a sort of starting over from scratch methodology, to avoid (as much as possible) any further confusion. Given that Google (in particular) has shown great interest in digitizing all forms of recorded media, I suggest a simple search+replace algorithm, locating all crystallography papers of the past 60 years in the great Googlebase (by the simple expedient of assuming that anything with the word crystallography in the title qualifies; the Google people may wish to participate in this effort), and then replacing any instances of the string right hand with the string left foot. I believe the concept of footedness will, in this way, catch on quickly, and readily address all of the problems brought forth by your research. I would hesitate to refer to this as my left footedness concept, but one is tempted... -- Steve Lane System, Network and Security Administrator Doudna Lab Biomolecular Structure and Mechanism Group UC Berkeley On Tue, Apr 01, 2008 at 10:59:34AM -0700, James Holton wrote: Dear CCP4BB, I think it prudent at this point for me to announce what could be a very old, but serious error in the fundamental mathematics of crystallography. To be brief, I have uncovered evidence that the hand of the micro-world is actually the opposite of what we have believed since Bijvoet's classic paper in 1951. Those of you who know me know that I have been trying to lay down the whole of x-ray diffraction into a single program. This is harder than it sounds. We all know what anomalous scattering is, but a detailed description of the math behind translating this dynamical theory effect all the way to the intensity of a particular detector pixel is hard to find all in one place. Most references in the literature about how anomalous scattering is connected to absolute configuration point to the classic Nature paper: Bijvoet et. al. (1951). Unfortunately, since this is a Nature paper, it is too short to describe the math in detail. For the calculations, the reader is referred to another paper by Bijvoet in the Proc. Roy. Acad. Amsterdam v52, 313 (1949). Essentially, the only new information in Bijvoet et. al. (1951) is the assertion that Emil Fischer got it right in his initial (arbitrary) assignment of the R and S reference compounds for the absolute configuration of molecules. I decided to follow this paper trail. The PRAA document was hard to come by and, to my disappointment, again referenced the real calculation to another work. Eventually, however, all roads lead back to R. W. James (1946). This is the definitive textbook on scattering theory (originally edited by Sir Lawrence Bragg himself). It is extremely useful, and I highly recommend that anyone who wants to really understand scattering should read it. However, even this wonderful text does not go through the full quantum-mechanical derivation of scattering, but rather rests on J. J. Thompson's original classical treatment. There is nothing wrong with this because the the exact value of the phase lag of the scattering event does not effect anything as long as the phase lag from all the atoms is the same. The only time it does become important is anomalous scattering. Even so, changing the sign of the phase lag will have no effect on any of the anomalous scattering equations as long as all the anomalous contributions have the same sign. The only time the sign of the phase lag is important is in the assignment of absolute configuration. Unfortunately, a full quantum
Re: [ccp4bb] into the looking glass
On Apr 1, 2008, at 5:52 PM, James Holton wrote: I myself am a left-handed human, and I admit I do find some devious pleasure in this reversal of fortunes. Perhaps it is some deep- seated suppressed anger from my days in kindergarten searching through piles of scissors for those few lefty ones that the oppressive rightist majority tossed into the pile to placate us. Even the lefties are envied by the ambidextrous. We don't know what hand we are at something until we try to do it. In kindergarten I was branded as left handed because that's how I held a pencil. Unfortunately, for cutting, it was the opposite. I was much older when I realized why those left handed scissors they gave me never worked so well--I was trying to use them with the wrong dang hand. If the ambidextrous had our way, the chirality of biological molecules would all be racemic. That would be true justice. James -- James Stroud UCLA-DOE Institute for Genomics and Proteomics 611 Charles E. Young Dr. S. Los Angeles, CA 90095 http://www.jamesstroud.com
