Re: [ccp4bb] chiral volumes--2nd try
Berhard, Then you have to define what you mean by smallest. SHELXL uses the (ASCII) alphabetical order of the three atom names for this purpose (SHELX manual page 7-23) so that it is unambiguous (since the names are not allowed to be the same), but presumably other programs use other conventions (e.g. the Cahn-Ingold-Prelog rules). George Prof. George M. Sheldrick FRS Dept. Structural Chemistry, University of Goettingen, Tammannstr. 4, D37077 Goettingen, Germany Tel. +49-551-39-3021 or -3068 Fax. +49-551-39-22582 On Mon, 19 Apr 2010, Bernhard Rupp wrote: The problem of discrete values in restraints can be circumvented by computing a corresponding continuous value such as a chiral volume Vc, which is given by a scalar triple vector product A (B x C) originating at the central atom. With the smallest ligand pointed toward the observer and clockwise assignment of the vectors, the sign of the chiral volume is positive, and computes to about 2.5 Å3. An alternative method of restraining chirality is by restraining the improper torsion (or improper dihedral or zeta-value) between CaNCCb to +34 deg. p 630 ;-) BR -Original Message- From: CCP4 bulletin board [mailto:ccp...@jiscmail.ac.uk] On Behalf Of Patrick Loll Sent: Monday, April 19, 2010 2:40 PM To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] chiral volumes--2nd try Sorry, the original post looks garbled (mirroring my internal state, no doubt). I'm trying again, sending as plain text: Friends, A question about the definition of chiral volumes: I'm looking for the definition of the SIGN of a chiral volume. The only ccp4 reference I can find (readily) is this: http://www.ysbl.york.ac.uk/~garib/refmac/docs/theory/chiral.html This page gives an algorithm for determining the sign, which I paraphrase here: * Call the central (chiral) carbon a, and its three non-hydrogen substituents b, c, and d. * Arrange things so that as you look from b to c to d, your eye is moving clockwise. * If atom a is below the plane formed by b, c, d, then the chiral volume is positive (otherwise negative) Clear enough. However, when I start to apply this rule to basically every library I have ever used, I get the opposite result. Try it, for example, with the ALA.cif file distributed with ccp4: _chem_comp_chir.comp_id _chem_comp_chir.id _chem_comp_chir.atom_id_centre _chem_comp_chir.atom_id_1 _chem_comp_chir.atom_id_2 _chem_comp_chir.atom_id_3 _chem_comp_chir.volume_sign ALA chir_01 CA N CB C negativ Assigning a as the centre atom and atoms b-d as numbers 1-3, when I apply the rule from the refmac page I get a positive chiral volume, not the negative one found in the cif file. Ditto for every other example that I have tried. Am I mis-reading what is meant by above and below? I'm assuming that if atoms b, c, and d all lie in a vertical plane, and you are facing that plane, then below means on the far side of that plane and above means between you and the plane. When I use the definition V1 * (V2 x V3), where V1 is vector FROM chiral atom to 1st substituent (e.g., CA to N in alanine example above), V2 = vector from chiral atom to 2nd substituent, etc., then I get the expected sign for the chiral volume. So is the refmac page wrong, or am I falling prey to some roaringly obvious stupidity? Having a rough Monday--starting to question my sanity. Thanks, Pat ps It appears that the term _chem_comp_chir.volume_sign is not defined in either the core or mmCIF dictionaries. Can this be right? --- Patrick J. Loll, Ph. D. Professor of Biochemistry Molecular Biology Director, Biochemistry Graduate Program Drexel University College of Medicine Room 10-102 New College Building 245 N. 15th St., Mailstop 497 Philadelphia, PA 19102-1192 USA (215) 762-7706 pat.l...@drexelmed.edu
Re: [ccp4bb] chiral volumes--2nd try
Then you have to define what you mean by smallest. Correct. A little manual reading often goes along way :-) br
Re: [ccp4bb] chiral volumes--2nd try
Dear Bernhard, You indeed have plenty of space to extend the margin notes on page 631! In the REFMAC monomer library that is also used by PHENIX, the sign of the chiral volume is explicitely defined for each chiral atom by _chem_comp_chir.volume_sign. For the L-aminoacids it is always defined by the order N CB C and the word negative. When I wrote SHELXL (long before REFMAC and PHENIX) I decided not to use any dictionaries; they often contain typos and I prefer to write stand-alone executables. I did not want the order of the atoms in the input file to influence the sign. So I used the ASCII (alphabetical) order of the atoms, and I defined the sign so that the L-amino-acids would all have positive C-alpha chiral volumes. Note that the Cahn-Ingold-Prelog rules make L-Cysteine R and the other 18 standard L-amino-acids S, which would be confusing. I suspect that the sequence rules described in the REFMAC documentation were not actually always used in determining the order of atoms specified in the monomer library. At least for the standard L-amino-acids (including CB of Thr and Ile) the sign is always opposite to that used by SHELXL. Note that the RTAB instuction in SHELXL can be used to print out chiral volumes without specifying the three bonded atoms, they are taken from the connectivity table. Best wishes, George Prof. George M. Sheldrick FRS Dept. Structural Chemistry, University of Goettingen, Tammannstr. 4, D37077 Goettingen, Germany Tel. +49-551-39-3021 or -3068 Fax. +49-551-39-22582 On Tue, 20 Apr 2010, Bernhard Rupp wrote: Actually, I have some space left under the figure caption this section refers to and will add the way SHELXL does it as another example. The CIPs are in a sidebar. Thx, BR -Original Message- From: CCP4 bulletin board [mailto:ccp...@jiscmail.ac.uk] On Behalf Of George M. Sheldrick Sent: Tuesday, April 20, 2010 12:17 AM To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] chiral volumes--2nd try Berhard, Then you have to define what you mean by smallest. SHELXL uses the (ASCII) alphabetical order of the three atom names for this purpose (SHELX manual page 7-23) so that it is unambiguous (since the names are not allowed to be the same), but presumably other programs use other conventions (e.g. the Cahn-Ingold-Prelog rules). George Prof. George M. Sheldrick FRS Dept. Structural Chemistry, University of Goettingen, Tammannstr. 4, D37077 Goettingen, Germany Tel. +49-551-39-3021 or -3068 Fax. +49-551-39-22582 On Mon, 19 Apr 2010, Bernhard Rupp wrote: The problem of discrete values in restraints can be circumvented by computing a corresponding continuous value such as a chiral volume Vc, which is given by a scalar triple vector product A ? (B x C) originating at the central atom. With the smallest ligand pointed toward the observer and clockwise assignment of the vectors, the sign of the chiral volume is positive, and computes to about 2.5 �3. An alternative method of restraining chirality is by restraining the improper torsion (or improper dihedral or zeta-value) between Ca?N?C?Cb to +34 deg. p 630 ;-) BR -Original Message- From: CCP4 bulletin board [mailto:ccp...@jiscmail.ac.uk] On Behalf Of Patrick Loll Sent: Monday, April 19, 2010 2:40 PM To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] chiral volumes--2nd try Sorry, the original post looks garbled (mirroring my internal state, no doubt). I'm trying again, sending as plain text: Friends, A question about the definition of chiral volumes: I'm looking for the definition of the SIGN of a chiral volume. The only ccp4 reference I can find (readily) is this: http://www.ysbl.york.ac.uk/~garib/refmac/docs/theory/chiral.html This page gives an algorithm for determining the sign, which I paraphrase here: * Call the central (chiral) carbon a, and its three non-hydrogen substituents b, c, and d. * Arrange things so that as you look from b to c to d, your eye is moving clockwise. * If atom a is below the plane formed by b, c, d, then the chiral volume is positive (otherwise negative) Clear enough. However, when I start to apply this rule to basically every library I have ever used, I get the opposite result. Try it, for example, with the ALA.cif file distributed with ccp4: _chem_comp_chir.comp_id _chem_comp_chir.id _chem_comp_chir.atom_id_centre _chem_comp_chir.atom_id_1 _chem_comp_chir.atom_id_2 _chem_comp_chir.atom_id_3 _chem_comp_chir.volume_sign ALA chir_01 CA N CB C negativ Assigning a as the centre atom and atoms b-d as numbers 1-3, when I apply the rule from the refmac page I get a positive chiral volume, not the negative one found in the cif file. Ditto for every other example that I have tried. Am I mis-reading what is meant by above and below? I'm
Re: [ccp4bb] chiral volumes--2nd try
For CB_ILE, the chiral volume sign in the REFMAC monomer library is the same as used by SHELXL, not the opposite as stated in my last posting. Apologies! George Prof. George M. Sheldrick FRS Dept. Structural Chemistry, University of Goettingen, Tammannstr. 4, D37077 Goettingen, Germany Tel. +49-551-39-3021 or -3068 Fax. +49-551-39-22582
Re: [ccp4bb] chiral volumes--2nd try
Joel, Agh. I can honestly say that this explanation never occurred to me, even though it is consistent with the data (But come on, any introductory organic chem text explains the R/S rules by moving from atom 2 to 3 to 4, and not by jumping from 2 to 4...surely you would follow the same convention in the refmac documentation, right?) What amazes me is my inability to find ANY documentation that actually explains the meaning of terms in the CIF used to define chiral volumes. OK, some of the terms ARE found in the mmCIF dictionary, but others seem made-up, like _chem_comp_chir.atom_id_1. Given that both refmac and phenix rely upon upon these libraries for determining geometries, you'd think that somewhere the terms would be defined explicitly. As several posters have pointed out, the triple scalar product is of course the correct way to define the chiral volume; but my point is that if you don't know which atoms the program is assigning to which vector, you're still in a pickle... Pat On 20 Apr 2010, at 3:51 PM, Bard, Joel wrote: Hi Patrick- I feel your pain having gone through exactly the same problem. It all has to do with the definition of When the eye goes from atom 2 to atom 4. I think we both assumed that this meant from 2 to 4 via 3 but I guess it doesn't. The ful text of my 2004 post: I think that two of the numbers are reversed in Figure 3 of the chiral center documentation for refmac5: http://www.ccp4.ac.uk/dist/html/refmac5/theory/chiral.html If one follows the Procedure to find the sign of a chiral centre with reference to the figure the eye would move from atom 2 through atom 3 to atom 4 as it traveled clockwise. This would generate a left handed coordinate system if atom 1 was behind the plane of the web browser so the sign of the chiral volume would be negative rather than positive as the text says. Switching the labels of atoms 2 and 3 (or 2 and 4 or 3 and 4 but 2 and 3 make it easier to visualize the right-hand-rule) would make it work. It seems like a very little thing but I'm feeble-minded enough to have spent more time than I'd like to admit trying to figure out why a little program I'd written was coming up with the wrong sign for the chiral volume when it had been correct the whole time. Of course I should have realized that it would be absurd for the statement: When the eye goes from atom2 to atom4 it should travel clockwise, to mean When the eye goes from atom2 to atom4 by passing through atom3 it should travel clockwise. It might be worth fixing, though, since I know for a fact that there are other people out there who are almost as easily confused as I am. Cheers, Joel --- Patrick J. Loll, Ph. D. Professor of Biochemistry Molecular Biology Director, Biochemistry Graduate Program Drexel University College of Medicine Room 10-102 New College Building 245 N. 15th St., Mailstop 497 Philadelphia, PA 19102-1192 USA (215) 762-7706 pat.l...@drexelmed.edu
Re: [ccp4bb] chiral volumes--2nd try
The problem of discrete values in restraints can be circumvented by computing a corresponding continuous value such as a chiral volume Vc, which is given by a scalar triple vector product A (B x C) originating at the central atom. With the smallest ligand pointed toward the observer and clockwise assignment of the vectors, the sign of the chiral volume is positive, and computes to about 2.5 Å3. An alternative method of restraining chirality is by restraining the improper torsion (or improper dihedral or zeta-value) between CaNCCb to +34 deg. p 630 ;-) BR -Original Message- From: CCP4 bulletin board [mailto:ccp...@jiscmail.ac.uk] On Behalf Of Patrick Loll Sent: Monday, April 19, 2010 2:40 PM To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] chiral volumes--2nd try Sorry, the original post looks garbled (mirroring my internal state, no doubt). I'm trying again, sending as plain text: Friends, A question about the definition of chiral volumes: I'm looking for the definition of the SIGN of a chiral volume. The only ccp4 reference I can find (readily) is this: http://www.ysbl.york.ac.uk/~garib/refmac/docs/theory/chiral.html This page gives an algorithm for determining the sign, which I paraphrase here: * Call the central (chiral) carbon a, and its three non-hydrogen substituents b, c, and d. * Arrange things so that as you look from b to c to d, your eye is moving clockwise. * If atom a is below the plane formed by b, c, d, then the chiral volume is positive (otherwise negative) Clear enough. However, when I start to apply this rule to basically every library I have ever used, I get the opposite result. Try it, for example, with the ALA.cif file distributed with ccp4: _chem_comp_chir.comp_id _chem_comp_chir.id _chem_comp_chir.atom_id_centre _chem_comp_chir.atom_id_1 _chem_comp_chir.atom_id_2 _chem_comp_chir.atom_id_3 _chem_comp_chir.volume_sign ALA chir_01 CA N CB C negativ Assigning a as the centre atom and atoms b-d as numbers 1-3, when I apply the rule from the refmac page I get a positive chiral volume, not the negative one found in the cif file. Ditto for every other example that I have tried. Am I mis-reading what is meant by above and below? I'm assuming that if atoms b, c, and d all lie in a vertical plane, and you are facing that plane, then below means on the far side of that plane and above means between you and the plane. When I use the definition V1 * (V2 x V3), where V1 is vector FROM chiral atom to 1st substituent (e.g., CA to N in alanine example above), V2 = vector from chiral atom to 2nd substituent, etc., then I get the expected sign for the chiral volume. So is the refmac page wrong, or am I falling prey to some roaringly obvious stupidity? Having a rough Monday--starting to question my sanity. Thanks, Pat ps It appears that the term _chem_comp_chir.volume_sign is not defined in either the core or mmCIF dictionaries. Can this be right? --- Patrick J. Loll, Ph. D. Professor of Biochemistry Molecular Biology Director, Biochemistry Graduate Program Drexel University College of Medicine Room 10-102 New College Building 245 N. 15th St., Mailstop 497 Philadelphia, PA 19102-1192 USA (215) 762-7706 pat.l...@drexelmed.edu
