Re: [ccp4bb] Lowering R factor from small molecule structure
I can help if share ,, no problem. Regards Umer On Fri, Jun 4, 2021, 7:39 PM Harry Powell - CCP4BB < 193323b1e616-dmarc-requ...@jiscmail.ac.uk> wrote: > I’d have to say that Phil is possibly one of the small molecule > crystallographers who could probably sort this out in a flash - hence my > last suggestion… > > Harry > > > On 4 Jun 2021, at 14:40, Phil Jeffrey wrote: > > > > Unlike macromolecular crystallography, small molecule crystallography is > infrequently starved for data. So it makes no sense at all to extend your > data to e.g. I/sigI of 1.0 amd Rmeas > 80% unless you want your R1 to be > >10% for no good reason or utility, which is what was behind my suggestion > - test to see if the data cutoff is an issue. Also about the fastest test > you can do in SHELXL. > > > > > Yes, ANIS and adding hydrogens (in SHELXL) are good things to do - > with 0.8Å data most small molecule crystallographers would do this as a > first step after fitting all the non-H atoms. > > > > Actually, adding AnisoB's and hydrogens too soon will mess up your > disorder modeling, so blanket statements like that work for well-behaved > structures but not so much for more challenging ones. > > > > e.g. in one of the the four structures I've done this week, one had > significant main-molecule disorder so that comes ahead of adding hydrogens, > and refining unrestrained anisoB (as is the default) for disordered atoms > is asking for trouble. It's not as cookie-cutter as you represent, and I > stick to all my suggestions. > > > > Phil Jeffrey > > Princeton > > > > On 6/4/21 4:27 AM, Harry Powell - CCP4BB wrote: > >> Hi > >> Yes, ANIS and adding hydrogens (in SHELXL) are good things to do - with > 0.8Å data most small molecule crystallographers would do this as a first > step after fitting all the non-H atoms. > >> One thing I can’t agree with is to cut the resolution of your data > _unless_ you have a very, very good reason to do so. Normal small molecule > refinements will use data to ~0.8Å and not use a cut-off based on > resolution or I/sig(I). A good dataset will often go to higher resolution > and small molecule crystallographers will be very happy to use these data > (unless, as I say, they have a very good reason not to), and would > certainly have to “explain to the referees” why they didn’t if they ignored > a systematic chunk. > >> Something else that you might not have thought of - have you actually > told SHELXL what the reflection data are - i.e., are they F, F^2, > intensity? It’s perfectly possible to solve a small molecule structure by > e.g. telling the program you’re giving it F^2 but actually giving it F, but > refinement would be somewhat less straightforward. SHELXL normally uses F^2 > in refinement, macromolecular programs still normally use F (AFAIK). > >> What programs did you use for processing the diffraction data? > >> Of course, lowering the R factor is not the objective of the exercise - > a lower R-factor is a consequence of having a model that fits the data > better. > >> I would be strongly inclined to ask a small molecule crystallographer > (or someone with a strong background in it) to have a look at your data & > model - they could probably give you a definitive answer by return of > e-mail. > >> Just my two ha’porth > >> Harry > >>> On 4 Jun 2021, at 03:10, Jon Cooper < > 488a26d62010-dmarc-requ...@jiscmail.ac.uk> wrote: > >>> > >>> Agreed, ANIS is the command to try. > >>> > >>> Sent from ProtonMail mobile > >>> > >>> > >>> > >>> Original Message > >>> On 3 Jun 2021, 20:18, Philip D. Jeffrey < pjeff...@princeton.edu> > wrote: > >>> > >>> R1 of 17% is bad for small molecule. > >>> 0.8 Å is in the eye of the beholder - if you're using macromolecular > cutoffs then these might be too aggressive for small molecule-type > refinement stats - try a more conservative cutoff lie 0.9 and see how that > changes R1. However I suspect it's more to do with how your model is > fitting the data. > >>> > >>> Have you refined anisotropic Bfactors ? > >>> Have you added hydrogens ? > >>> > >>> I would suggest non-CCP4 programs like Olex2 or SHELXLE as the > interface for the refinements - I use the latter and it's somewhat Coot > like with useful features that are particular to small molecule. Also > PLATON has some things (like expand-to-P1 and Squeeze) that, respectively, > might be useful to explore space group issues and dis
Re: [ccp4bb] Lowering R factor from small molecule structure
I’d have to say that Phil is possibly one of the small molecule crystallographers who could probably sort this out in a flash - hence my last suggestion… Harry > On 4 Jun 2021, at 14:40, Phil Jeffrey wrote: > > Unlike macromolecular crystallography, small molecule crystallography is > infrequently starved for data. So it makes no sense at all to extend your > data to e.g. I/sigI of 1.0 amd Rmeas > 80% unless you want your R1 to be >10% > for no good reason or utility, which is what was behind my suggestion - test > to see if the data cutoff is an issue. Also about the fastest test you can > do in SHELXL. > > > Yes, ANIS and adding hydrogens (in SHELXL) are good things to do - with > > 0.8Å data most small molecule crystallographers would do this as a first > > step after fitting all the non-H atoms. > > Actually, adding AnisoB's and hydrogens too soon will mess up your disorder > modeling, so blanket statements like that work for well-behaved structures > but not so much for more challenging ones. > > e.g. in one of the the four structures I've done this week, one had > significant main-molecule disorder so that comes ahead of adding hydrogens, > and refining unrestrained anisoB (as is the default) for disordered atoms is > asking for trouble. It's not as cookie-cutter as you represent, and I stick > to all my suggestions. > > Phil Jeffrey > Princeton > > On 6/4/21 4:27 AM, Harry Powell - CCP4BB wrote: >> Hi >> Yes, ANIS and adding hydrogens (in SHELXL) are good things to do - with 0.8Å >> data most small molecule crystallographers would do this as a first step >> after fitting all the non-H atoms. >> One thing I can’t agree with is to cut the resolution of your data _unless_ >> you have a very, very good reason to do so. Normal small molecule >> refinements will use data to ~0.8Å and not use a cut-off based on resolution >> or I/sig(I). A good dataset will often go to higher resolution and small >> molecule crystallographers will be very happy to use these data (unless, as >> I say, they have a very good reason not to), and would certainly have to >> “explain to the referees” why they didn’t if they ignored a systematic chunk. >> Something else that you might not have thought of - have you actually told >> SHELXL what the reflection data are - i.e., are they F, F^2, intensity? It’s >> perfectly possible to solve a small molecule structure by e.g. telling the >> program you’re giving it F^2 but actually giving it F, but refinement would >> be somewhat less straightforward. SHELXL normally uses F^2 in refinement, >> macromolecular programs still normally use F (AFAIK). >> What programs did you use for processing the diffraction data? >> Of course, lowering the R factor is not the objective of the exercise - a >> lower R-factor is a consequence of having a model that fits the data better. >> I would be strongly inclined to ask a small molecule crystallographer (or >> someone with a strong background in it) to have a look at your data & model >> - they could probably give you a definitive answer by return of e-mail. >> Just my two ha’porth >> Harry >>> On 4 Jun 2021, at 03:10, Jon Cooper >>> <488a26d62010-dmarc-requ...@jiscmail.ac.uk> wrote: >>> >>> Agreed, ANIS is the command to try. >>> >>> Sent from ProtonMail mobile >>> >>> >>> >>> Original Message >>> On 3 Jun 2021, 20:18, Philip D. Jeffrey < pjeff...@princeton.edu> wrote: >>> >>> R1 of 17% is bad for small molecule. >>> 0.8 Å is in the eye of the beholder - if you're using macromolecular >>> cutoffs then these might be too aggressive for small molecule-type >>> refinement stats - try a more conservative cutoff lie 0.9 and see how that >>> changes R1. However I suspect it's more to do with how your model is >>> fitting the data. >>> >>> Have you refined anisotropic Bfactors ? >>> Have you added hydrogens ? >>> >>> I would suggest non-CCP4 programs like Olex2 or SHELXLE as the interface >>> for the refinements - I use the latter and it's somewhat Coot like with >>> useful features that are particular to small molecule. Also PLATON has >>> some things (like expand-to-P1 and Squeeze) that, respectively, might be >>> useful to explore space group issues and disordered solvent. PLATON also >>> has a means to check for some forms of twinning. >>> >>> Phil Jeffrey >>> Princeton >>> From: CCP4 bulletin board on behalf of Jacob >>
Re: [ccp4bb] Lowering R factor from small molecule structure
Twinning disorders solvent and hydrogen atoms position with adjustment of several factors, small molecules are no so complicated as macromolecules. Regards Umer On Fri, Jun 4, 2021, 6:41 PM Phil Jeffrey wrote: > Unlike macromolecular crystallography, small molecule crystallography is > infrequently starved for data. So it makes no sense at all to extend > your data to e.g. I/sigI of 1.0 amd Rmeas > 80% unless you want your R1 > to be >10% for no good reason or utility, which is what was behind my > suggestion - test to see if the data cutoff is an issue. Also about the > fastest test you can do in SHELXL. > > > Yes, ANIS and adding hydrogens (in SHELXL) are good things to do - > with 0.8Å data most small molecule crystallographers would do this as a > first step after fitting all the non-H atoms. > > Actually, adding AnisoB's and hydrogens too soon will mess up your > disorder modeling, so blanket statements like that work for well-behaved > structures but not so much for more challenging ones. > > e.g. in one of the the four structures I've done this week, one had > significant main-molecule disorder so that comes ahead of adding > hydrogens, and refining unrestrained anisoB (as is the default) for > disordered atoms is asking for trouble. It's not as cookie-cutter as > you represent, and I stick to all my suggestions. > > Phil Jeffrey > Princeton > > On 6/4/21 4:27 AM, Harry Powell - CCP4BB wrote: > > Hi > > > > Yes, ANIS and adding hydrogens (in SHELXL) are good things to do - with > 0.8Å data most small molecule crystallographers would do this as a first > step after fitting all the non-H atoms. > > > > One thing I can’t agree with is to cut the resolution of your data > _unless_ you have a very, very good reason to do so. Normal small molecule > refinements will use data to ~0.8Å and not use a cut-off based on > resolution or I/sig(I). A good dataset will often go to higher resolution > and small molecule crystallographers will be very happy to use these data > (unless, as I say, they have a very good reason not to), and would > certainly have to “explain to the referees” why they didn’t if they ignored > a systematic chunk. > > > > Something else that you might not have thought of - have you actually > told SHELXL what the reflection data are - i.e., are they F, F^2, > intensity? It’s perfectly possible to solve a small molecule structure by > e.g. telling the program you’re giving it F^2 but actually giving it F, but > refinement would be somewhat less straightforward. SHELXL normally uses F^2 > in refinement, macromolecular programs still normally use F (AFAIK). > > > > What programs did you use for processing the diffraction data? > > > > Of course, lowering the R factor is not the objective of the exercise - > a lower R-factor is a consequence of having a model that fits the data > better. > > > > I would be strongly inclined to ask a small molecule crystallographer > (or someone with a strong background in it) to have a look at your data & > model - they could probably give you a definitive answer by return of > e-mail. > > > > Just my two ha’porth > > > > Harry > > > >> On 4 Jun 2021, at 03:10, Jon Cooper < > 488a26d62010-dmarc-requ...@jiscmail.ac.uk> wrote: > >> > >> Agreed, ANIS is the command to try. > >> > >> Sent from ProtonMail mobile > >> > >> > >> > >> Original Message > >> On 3 Jun 2021, 20:18, Philip D. Jeffrey < pjeff...@princeton.edu> > wrote: > >> > >> R1 of 17% is bad for small molecule. > >> 0.8 Å is in the eye of the beholder - if you're using macromolecular > cutoffs then these might be too aggressive for small molecule-type > refinement stats - try a more conservative cutoff lie 0.9 and see how that > changes R1. However I suspect it's more to do with how your model is > fitting the data. > >> > >> Have you refined anisotropic Bfactors ? > >> Have you added hydrogens ? > >> > >> I would suggest non-CCP4 programs like Olex2 or SHELXLE as the > interface for the refinements - I use the latter and it's somewhat Coot > like with useful features that are particular to small molecule. Also > PLATON has some things (like expand-to-P1 and Squeeze) that, respectively, > might be useful to explore space group issues and disordered solvent. > PLATON also has a means to check for some forms of twinning. > >> > >> Phil Jeffrey > >> Princeton > >> From: CCP4 bulletin board on behalf of Jacob > Summers <60a137e4bf3a-dmarc-requ...@jiscmail.ac.uk> > >
Re: [ccp4bb] Lowering R factor from small molecule structure
Unlike macromolecular crystallography, small molecule crystallography is infrequently starved for data. So it makes no sense at all to extend your data to e.g. I/sigI of 1.0 amd Rmeas > 80% unless you want your R1 to be >10% for no good reason or utility, which is what was behind my suggestion - test to see if the data cutoff is an issue. Also about the fastest test you can do in SHELXL. > Yes, ANIS and adding hydrogens (in SHELXL) are good things to do - with 0.8Å data most small molecule crystallographers would do this as a first step after fitting all the non-H atoms. Actually, adding AnisoB's and hydrogens too soon will mess up your disorder modeling, so blanket statements like that work for well-behaved structures but not so much for more challenging ones. e.g. in one of the the four structures I've done this week, one had significant main-molecule disorder so that comes ahead of adding hydrogens, and refining unrestrained anisoB (as is the default) for disordered atoms is asking for trouble. It's not as cookie-cutter as you represent, and I stick to all my suggestions. Phil Jeffrey Princeton On 6/4/21 4:27 AM, Harry Powell - CCP4BB wrote: Hi Yes, ANIS and adding hydrogens (in SHELXL) are good things to do - with 0.8Å data most small molecule crystallographers would do this as a first step after fitting all the non-H atoms. One thing I can’t agree with is to cut the resolution of your data _unless_ you have a very, very good reason to do so. Normal small molecule refinements will use data to ~0.8Å and not use a cut-off based on resolution or I/sig(I). A good dataset will often go to higher resolution and small molecule crystallographers will be very happy to use these data (unless, as I say, they have a very good reason not to), and would certainly have to “explain to the referees” why they didn’t if they ignored a systematic chunk. Something else that you might not have thought of - have you actually told SHELXL what the reflection data are - i.e., are they F, F^2, intensity? It’s perfectly possible to solve a small molecule structure by e.g. telling the program you’re giving it F^2 but actually giving it F, but refinement would be somewhat less straightforward. SHELXL normally uses F^2 in refinement, macromolecular programs still normally use F (AFAIK). What programs did you use for processing the diffraction data? Of course, lowering the R factor is not the objective of the exercise - a lower R-factor is a consequence of having a model that fits the data better. I would be strongly inclined to ask a small molecule crystallographer (or someone with a strong background in it) to have a look at your data & model - they could probably give you a definitive answer by return of e-mail. Just my two ha’porth Harry On 4 Jun 2021, at 03:10, Jon Cooper <488a26d62010-dmarc-requ...@jiscmail.ac.uk> wrote: Agreed, ANIS is the command to try. Sent from ProtonMail mobile Original Message On 3 Jun 2021, 20:18, Philip D. Jeffrey < pjeff...@princeton.edu> wrote: R1 of 17% is bad for small molecule. 0.8 Å is in the eye of the beholder - if you're using macromolecular cutoffs then these might be too aggressive for small molecule-type refinement stats - try a more conservative cutoff lie 0.9 and see how that changes R1. However I suspect it's more to do with how your model is fitting the data. Have you refined anisotropic Bfactors ? Have you added hydrogens ? I would suggest non-CCP4 programs like Olex2 or SHELXLE as the interface for the refinements - I use the latter and it's somewhat Coot like with useful features that are particular to small molecule. Also PLATON has some things (like expand-to-P1 and Squeeze) that, respectively, might be useful to explore space group issues and disordered solvent. PLATON also has a means to check for some forms of twinning. Phil Jeffrey Princeton From: CCP4 bulletin board on behalf of Jacob Summers <60a137e4bf3a-dmarc-requ...@jiscmail.ac.uk> Sent: Thursday, June 3, 2021 2:49 PM To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] Lowering R factor from small molecule structure Greetings! I am currently trying to reduce the R factor of a cyclic small molecule peptoid in ShelXle. The max resolution of the molecule is 0.8 angstroms. The molecule itself fits the density very well, but there are a few unexplained densities around the molecule which do not seem to be anything in the crystallization conditions. The R1 factor of the refinement is 17.07% but I am unsure how to lower this value. Any ideas on how to better refine this molecule or fill densities to lower the R1 factor? I do not have much experience working with small molecule refinement or with ShelX. Thanks so much, Jacob Summers To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.a
Re: [ccp4bb] Lowering R factor from small molecule structure
Hi Yes, ANIS and adding hydrogens (in SHELXL) are good things to do - with 0.8Å data most small molecule crystallographers would do this as a first step after fitting all the non-H atoms. One thing I can’t agree with is to cut the resolution of your data _unless_ you have a very, very good reason to do so. Normal small molecule refinements will use data to ~0.8Å and not use a cut-off based on resolution or I/sig(I). A good dataset will often go to higher resolution and small molecule crystallographers will be very happy to use these data (unless, as I say, they have a very good reason not to), and would certainly have to “explain to the referees” why they didn’t if they ignored a systematic chunk. Something else that you might not have thought of - have you actually told SHELXL what the reflection data are - i.e., are they F, F^2, intensity? It’s perfectly possible to solve a small molecule structure by e.g. telling the program you’re giving it F^2 but actually giving it F, but refinement would be somewhat less straightforward. SHELXL normally uses F^2 in refinement, macromolecular programs still normally use F (AFAIK). What programs did you use for processing the diffraction data? Of course, lowering the R factor is not the objective of the exercise - a lower R-factor is a consequence of having a model that fits the data better. I would be strongly inclined to ask a small molecule crystallographer (or someone with a strong background in it) to have a look at your data & model - they could probably give you a definitive answer by return of e-mail. Just my two ha’porth Harry > On 4 Jun 2021, at 03:10, Jon Cooper > <488a26d62010-dmarc-requ...@jiscmail.ac.uk> wrote: > > Agreed, ANIS is the command to try. > > Sent from ProtonMail mobile > > > > Original Message > On 3 Jun 2021, 20:18, Philip D. Jeffrey < pjeff...@princeton.edu> wrote: > > R1 of 17% is bad for small molecule. > 0.8 Å is in the eye of the beholder - if you're using macromolecular cutoffs > then these might be too aggressive for small molecule-type refinement stats - > try a more conservative cutoff lie 0.9 and see how that changes R1. However > I suspect it's more to do with how your model is fitting the data. > > Have you refined anisotropic Bfactors ? > Have you added hydrogens ? > > I would suggest non-CCP4 programs like Olex2 or SHELXLE as the interface for > the refinements - I use the latter and it's somewhat Coot like with useful > features that are particular to small molecule. Also PLATON has some things > (like expand-to-P1 and Squeeze) that, respectively, might be useful to > explore space group issues and disordered solvent. PLATON also has a means > to check for some forms of twinning. > > Phil Jeffrey > Princeton > From: CCP4 bulletin board on behalf of Jacob Summers > <60a137e4bf3a-dmarc-requ...@jiscmail.ac.uk> > Sent: Thursday, June 3, 2021 2:49 PM > To: CCP4BB@JISCMAIL.AC.UK > Subject: [ccp4bb] Lowering R factor from small molecule structure > > Greetings! > > I am currently trying to reduce the R factor of a cyclic small molecule > peptoid in ShelXle. The max resolution of the molecule is 0.8 angstroms. The > molecule itself fits the density very well, but there are a few unexplained > densities around the molecule which do not seem to be anything in the > crystallization conditions. The R1 factor of the refinement is 17.07% but I > am unsure how to lower this value. Any ideas on how to better refine this > molecule or fill densities to lower the R1 factor? I do not have much > experience working with small molecule refinement or with ShelX. > > Thanks so much, > Jacob Summers > > > > To unsubscribe from the CCP4BB list, click the following link: > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 > > This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing > list hosted by www.jiscmail.ac.uk, terms & conditions are available at > https://www.jiscmail.ac.uk/policyandsecurity/ > > To unsubscribe from the CCP4BB list, click the following link: > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 > > To unsubscribe from the CCP4BB list, click the following link: > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
Re: [ccp4bb] Lowering R factor from small molecule structure
Agreed, ANIS is the command to try. Sent from ProtonMail mobile Original Message On 3 Jun 2021, 20:18, Philip D. Jeffrey wrote: > R1 of 17% is bad for small molecule. > 0.8 Å is in the eye of the beholder - if you're using macromolecular cutoffs > then these might be too aggressive for small molecule-type refinement stats - > try a more conservative cutoff lie 0.9 and see how that changes R1. However I > suspect it's more to do with how your model is fitting the data. > > Have you refined anisotropic Bfactors ? > Have you added hydrogens ? > > I would suggest non-CCP4 programs like Olex2 or SHELXLE as the interface for > the refinements - I use the latter and it's somewhat Coot like with useful > features that are particular to small molecule. Also PLATON has some things > (like expand-to-P1 and Squeeze) that, respectively, might be useful to > explore space group issues and disordered solvent. PLATON also has a means to > check for some forms of twinning. > > Phil Jeffrey > Princeton > > --- > > From: CCP4 bulletin board on behalf of Jacob Summers > <60a137e4bf3a-dmarc-requ...@jiscmail.ac.uk> > Sent: Thursday, June 3, 2021 2:49 PM > To: CCP4BB@JISCMAIL.AC.UK > Subject: [ccp4bb] Lowering R factor from small molecule structure > > Greetings! > > I am currently trying to reduce the R factor of a cyclic small molecule > peptoid in ShelXle. The max resolution of the molecule is 0.8 angstroms. The > molecule itself fits the density very well, but there are a few unexplained > densities around the molecule which do not seem to be anything in the > crystallization conditions. The R1 factor of the refinement is 17.07% but I > am unsure how to lower this value. Any ideas on how to better refine this > molecule or fill densities to lower the R1 factor? I do not have much > experience working with small molecule refinement or with ShelX. > > Thanks so much, > Jacob Summers > > > > To unsubscribe from the CCP4BB list, click the following link: > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 > > This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing > list hosted by www.jiscmail.ac.uk, terms & conditions are available at > https://www.jiscmail.ac.uk/policyandsecurity/ > > --- > > To unsubscribe from the CCP4BB list, click the following link: > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
Re: [ccp4bb] Lowering R factor from small molecule structure
Hi Jacob, >>The systematic absences in the hkl file pointed to P212121 being the space group, which is what it was processed in. If the data were processed in this space group (Laue class), the analysis of the systematic absence won't tell anything else. Probably, it would be more useful to process data in P1 and then rerun space-group determination. It would be useful to look at some statistics in the processed data, particularly the R(int) and the R(sigma) values. Since the R(int) is a measure of reproducibility, high values can mean the Laue group is wrong, poor/no absorption corrections, crystal twinning or disorder etc. R(sigma) relates to the signal-to-noise ratio of the data, and the R1 should stay close to R(sigma) in a rough estimate. Also, If R(int) is much greater than R(sigma) (say, 2 - 3 times), that usually indicates a problem in data. If you have access to diffraction images, look at several of them for possible disorder or twinning. If you have got good data, then you can look for further problems in the model. HTH, Rangana On Thu, Jun 3, 2021 at 8:45 PM Jacob Summers < 60a137e4bf3a-dmarc-requ...@jiscmail.ac.uk> wrote: > The systematic absences in the hkl file pointed to P212121 being the space > group, which is what it was processed in. As for the peaks, the highest > peaks are 3.92 at 2.72 A from an oxygen (Q1), 3.67 at 2.74 A from an oxygen > (Q2), and 2.68 at 2.75 A from an oxygen (Q3). Q1 and Q3 seem to be about > 2.82 A from each other and both appear to coordinate in the center of the > cyclic molecule. Filling these densities decreases the R1 value, but the > atoms do not refine well. I have been using ShelXle for refinements and > visualization but am new to the software and small molecule refinement. > > Thanks, > Jacob > > > > To unsubscribe from the CCP4BB list, click the following link: > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 > > This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a > mailing list hosted by www.jiscmail.ac.uk, terms & conditions are > available at https://www.jiscmail.ac.uk/policyandsecurity/ > To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
Re: [ccp4bb] Lowering R factor from small molecule structure
The systematic absences in the hkl file pointed to P212121 being the space group, which is what it was processed in. As for the peaks, the highest peaks are 3.92 at 2.72 A from an oxygen (Q1), 3.67 at 2.74 A from an oxygen (Q2), and 2.68 at 2.75 A from an oxygen (Q3). Q1 and Q3 seem to be about 2.82 A from each other and both appear to coordinate in the center of the cyclic molecule. Filling these densities decreases the R1 value, but the atoms do not refine well. I have been using ShelXle for refinements and visualization but am new to the software and small molecule refinement. Thanks, Jacob To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
Re: [ccp4bb] Lowering R factor from small molecule structure
R1 of 17% is bad for small molecule. 0.8 Å is in the eye of the beholder - if you're using macromolecular cutoffs then these might be too aggressive for small molecule-type refinement stats - try a more conservative cutoff lie 0.9 and see how that changes R1. However I suspect it's more to do with how your model is fitting the data. Have you refined anisotropic Bfactors ? Have you added hydrogens ? I would suggest non-CCP4 programs like Olex2 or SHELXLE as the interface for the refinements - I use the latter and it's somewhat Coot like with useful features that are particular to small molecule. Also PLATON has some things (like expand-to-P1 and Squeeze) that, respectively, might be useful to explore space group issues and disordered solvent. PLATON also has a means to check for some forms of twinning. Phil Jeffrey Princeton From: CCP4 bulletin board on behalf of Jacob Summers <60a137e4bf3a-dmarc-requ...@jiscmail.ac.uk> Sent: Thursday, June 3, 2021 2:49 PM To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] Lowering R factor from small molecule structure Greetings! I am currently trying to reduce the R factor of a cyclic small molecule peptoid in ShelXle. The max resolution of the molecule is 0.8 angstroms. The molecule itself fits the density very well, but there are a few unexplained densities around the molecule which do not seem to be anything in the crystallization conditions. The R1 factor of the refinement is 17.07% but I am unsure how to lower this value. Any ideas on how to better refine this molecule or fill densities to lower the R1 factor? I do not have much experience working with small molecule refinement or with ShelX. Thanks so much, Jacob Summers To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB<http://www.jiscmail.ac.uk/CCP4BB>, a mailing list hosted by www.jiscmail.ac.uk<http://www.jiscmail.ac.uk>, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/ To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
Re: [ccp4bb] Lowering R factor from small molecule structure
Dear Jacob, An R-value of 17% is indeed suspiciously high for a small molecule structure. Some thoughts: Are you sure the space group is correct? There might be twinning involved,. Have you checked the ’signs of twinning’ for small molecules? There might be disordered solvent molecules, which could be modeled, although that’s not always trivial nor possible. How high are the residual peaks? This could give you info about what’s out there? If the residual peaks are located very close to heavy atoms, the data might suffer (severely) from absorption. Regards Kristof > On 3 Jun 2021, at 20:49, Jacob Summers > <60a137e4bf3a-dmarc-requ...@jiscmail.ac.uk> wrote: > > Greetings! > > I am currently trying to reduce the R factor of a cyclic small molecule > peptoid in ShelXle. The max resolution of the molecule is 0.8 angstroms. The > molecule itself fits the density very well, but there are a few unexplained > densities around the molecule which do not seem to be anything in the > crystallization conditions. The R1 factor of the refinement is 17.07% but I > am unsure how to lower this value. Any ideas on how to better refine this > molecule or fill densities to lower the R1 factor? I do not have much > experience working with small molecule refinement or with ShelX. > > Thanks so much, > Jacob Summers > > > > To unsubscribe from the CCP4BB list, click the following link: > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 > > This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing > list hosted by www.jiscmail.ac.uk, terms & conditions are available at > https://www.jiscmail.ac.uk/policyandsecurity/ To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
[ccp4bb] Lowering R factor from small molecule structure
Greetings! I am currently trying to reduce the R factor of a cyclic small molecule peptoid in ShelXle. The max resolution of the molecule is 0.8 angstroms. The molecule itself fits the density very well, but there are a few unexplained densities around the molecule which do not seem to be anything in the crystallization conditions. The R1 factor of the refinement is 17.07% but I am unsure how to lower this value. Any ideas on how to better refine this molecule or fill densities to lower the R1 factor? I do not have much experience working with small molecule refinement or with ShelX. Thanks so much, Jacob Summers To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
