Re: [ccp4bb] Alternate sugar conformations in refmac 5.5.0110
Hi Markus, I had a brief look at the structure fragment that you had included in your mail, and I don't think that you really observe these two conformations. Stereochemistry of the A conformation looks fine, but the sugar in the alternate B conformation is not an NAG but an NDG (i.e. it has an alpha-linkage, not a beta-linkage). In N-glycans, however, the GlcNAc residues are always in beta anomeric conformation in nature. Therefore I recommend to exclude the alternate B conformation (atoms 139-152) from your structure. By the way, the ring shapes of the sugars look twisted, maybe that is a result of the produced overlap in the coordinates? Best regards, Thomas
Re: [ccp4bb] Alternate sugar conformations in refmac 5.5.0110
Hi Robbie, Oops, sorry, I used CCP4 6.3: Refmac_5.7.0032 version 5.7.0032 : 05/09/12 (confirmed by the log file) so I am using the current version and the problem still persists. Thanks! Markus On 18/04/13 03:31 PM, Robbie Joosten wrote: > Hi Markus, > > You could try changing your Refmac version. The version you are using is > ancient. You may have an old version in your > PATH next to the new one because your CCP4 seems up to date. > > AFAICT there is nothing wrong with the LINKR or the HETATM records > > Sent from my Windows Phone > > From: Markus Meier > Sent: 2013-04-18 22:19 > To: CCP4BB@JISCMAIL.AC.UK > Subject: [ccp4bb] Alternate sugar conformations in refmac 5.5.0110 > > Dear all, > > I am trying to refine a beta-D-N-Acetyl glucosamine moiety (NAG) linked > to an asparagine (ASN) in Refmac. > (version CCP4 6.3: Refmac_5.5.0110 version 5.5.0110 : 08/05/10) > > The sugar has two alternate conformations that occupy the same position in > the electron > density but are rotated 180° relative to each other. Even though I have > defined two alternate conformations for the asparagine side chain, the > sugar and the beta-link, Refmac pushes the two conformations apart, out of > the electron > density (while still honouring the link to Asn). So it seems that Refmac > applies repulsive > forces between the alternate conformations. > > Did anyone else experience this and/or can suggest a fix? > All help is very much appreciated! > > My definitions for the alternate conformations in the PDB file are below: > > LINKRC1 ANAG E 1 ND2AASN A 116 > NAG-ASN > LINKRC1 BNAG E 1 ND2BASN A 116 > NAG-ASN > HETATM 125 C1 ANAG E 1 30.978 40.626 -25.446 0.50 98.96 EC > HETATM 126 C2 ANAG E 1 30.428 41.897 -26.138 0.50100.81 EC > HETATM 127 N2 ANAG E 1 29.783 41.751 -27.447 0.50 94.26 EN > HETATM 128 C7 ANAG E 1 28.807 42.561 -27.924 0.50 89.45 EC > HETATM 129 O7 ANAG E 1 28.325 42.377 -29.035 0.50 83.16 EO > HETATM 130 C8 ANAG E 1 28.252 43.720 -27.128 0.50 87.63 EC > HETATM 131 C3 ANAG E 1 31.618 42.847 -26.221 0.50102.77 EC > HETATM 132 O3 ANAG E 1 31.420 43.888 -27.159 0.50102.25 EO > HETATM 133 C4 ANAG E 1 31.840 43.369 -24.802 0.50103.37 EC > HETATM 134 O4 ANAG E 1 32.969 44.217 -24.782 0.50104.91 EO > HETATM 135 C5 ANAG E 1 32.040 42.223 -23.785 0.50 94.99 EC > HETATM 136 C6 ANAG E 1 31.564 42.633 -22.381 0.50 86.60 EC > HETATM 137 O6 ANAG E 1 32.632 42.591 -21.462 0.50 77.76 EO > HETATM 138 O5 ANAG E 1 31.458 40.954 -24.130 0.50 99.19 EO > HETATM 139 C1 BNAG E 1 30.271 40.925 -24.108 0.50 98.96 EC > HETATM 140 C2 BNAG E 1 31.415 41.878 -23.684 0.50100.81 EC > HETATM 141 N2 BNAG E 1 32.048 41.664 -22.378 0.50 94.26 EN > HETATM 142 C7 BNAG E 1 33.331 41.981 -22.079 0.50 89.45 EC > HETATM 143 O7 BNAG E 1 33.784 41.778 -20.959 0.50 83.16 EO > HETATM 144 C8 BNAG E 1 34.276 42.586 -23.092 0.50 87.63 EC > HETATM 145 C3 BNAG E 1 30.816 43.277 -23.775 0.50102.77 EC > HETATM 146 O3 BNAG E 1 31.569 44.240 -23.061 0.50102.25 EO > HETATM 147 C4 BNAG E 1 30.718 43.597 -25.266 0.50103.37 EC > HETATM 148 O4 BNAG E 1 30.115 44.862 -25.440 0.50104.91 EO > HETATM 149 C5 BNAG E 1 29.907 42.532 -26.038 0.50 94.99 EC > HETATM 150 C6 BNAG E 1 30.373 42.426 -27.500 0.50 86.60 EC > HETATM 151 O6 BNAG E 1 29.320 42.743 -28.381 0.50 77.76 EO > HETATM 152 O5 BNAG E 1 29.866 41.216 -25.458 0.50 99.19 EO > ATOM745 N ASN A 116 27.207 36.475 -25.453 1.00 62.15 AN > ATOM746 CA AASN A 116 28.475 37.144 -25.135 0.50 61.77 AC > ATOM747 CB AASN A 116 28.182 38.336 -24.223 0.50 69.02 AC > ATOM748 CG AASN A 116 29.037 39.555 -24.495 0.50 79.45 AC > ATOM749 OD1AASN A 116 28.656 40.644 -24.047 0.50 83.18 AO > ATOM750 ND2AASN A 116 30.178 39.419 -25.218 0.50 87.72 AN > ATOM751 C ASN A 116 29.353 36.143 -24.389 1.00 53.28 AC > ATOM752 O ASN A 116 29.778 36.380 -23.266 1.00 48.83 AO > ATOM753 CA BASN A 116 28.575 37.144 -25.135 0.50 61.77 AC > ATOM754 CB BASN A 116 28.282 38.336 -24.223 0.50 69.02 AC > ATOM755 CG BASN A 116 29.487 39.201 -23.920 0.50 79.45
Re: [ccp4bb] Alternate sugar conformations in refmac 5.5.0110
Hi Markus, You could try changing your Refmac version. The version you are using is ancient. You may have an old version in your PATH next to the new one because your CCP4 seems up to date. AFAICT there is nothing wrong with the LINKR or the HETATM records Sent from my Windows Phone From: Markus Meier Sent: 2013-04-18 22:19 To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] Alternate sugar conformations in refmac 5.5.0110 Dear all, I am trying to refine a beta-D-N-Acetyl glucosamine moiety (NAG) linked to an asparagine (ASN) in Refmac. (version CCP4 6.3: Refmac_5.5.0110 version 5.5.0110 : 08/05/10) The sugar has two alternate conformations that occupy the same position in the electron density but are rotated 180° relative to each other. Even though I have defined two alternate conformations for the asparagine side chain, the sugar and the beta-link, Refmac pushes the two conformations apart, out of the electron density (while still honouring the link to Asn). So it seems that Refmac applies repulsive forces between the alternate conformations. Did anyone else experience this and/or can suggest a fix? All help is very much appreciated! My definitions for the alternate conformations in the PDB file are below: LINKRC1 ANAG E 1 ND2AASN A 116NAG-ASN LINKRC1 BNAG E 1 ND2BASN A 116NAG-ASN HETATM 125 C1 ANAG E 1 30.978 40.626 -25.446 0.50 98.96 EC HETATM 126 C2 ANAG E 1 30.428 41.897 -26.138 0.50100.81 EC HETATM 127 N2 ANAG E 1 29.783 41.751 -27.447 0.50 94.26 EN HETATM 128 C7 ANAG E 1 28.807 42.561 -27.924 0.50 89.45 EC HETATM 129 O7 ANAG E 1 28.325 42.377 -29.035 0.50 83.16 EO HETATM 130 C8 ANAG E 1 28.252 43.720 -27.128 0.50 87.63 EC HETATM 131 C3 ANAG E 1 31.618 42.847 -26.221 0.50102.77 EC HETATM 132 O3 ANAG E 1 31.420 43.888 -27.159 0.50102.25 EO HETATM 133 C4 ANAG E 1 31.840 43.369 -24.802 0.50103.37 EC HETATM 134 O4 ANAG E 1 32.969 44.217 -24.782 0.50104.91 EO HETATM 135 C5 ANAG E 1 32.040 42.223 -23.785 0.50 94.99 EC HETATM 136 C6 ANAG E 1 31.564 42.633 -22.381 0.50 86.60 EC HETATM 137 O6 ANAG E 1 32.632 42.591 -21.462 0.50 77.76 EO HETATM 138 O5 ANAG E 1 31.458 40.954 -24.130 0.50 99.19 EO HETATM 139 C1 BNAG E 1 30.271 40.925 -24.108 0.50 98.96 EC HETATM 140 C2 BNAG E 1 31.415 41.878 -23.684 0.50100.81 EC HETATM 141 N2 BNAG E 1 32.048 41.664 -22.378 0.50 94.26 EN HETATM 142 C7 BNAG E 1 33.331 41.981 -22.079 0.50 89.45 EC HETATM 143 O7 BNAG E 1 33.784 41.778 -20.959 0.50 83.16 EO HETATM 144 C8 BNAG E 1 34.276 42.586 -23.092 0.50 87.63 EC HETATM 145 C3 BNAG E 1 30.816 43.277 -23.775 0.50102.77 EC HETATM 146 O3 BNAG E 1 31.569 44.240 -23.061 0.50102.25 EO HETATM 147 C4 BNAG E 1 30.718 43.597 -25.266 0.50103.37 EC HETATM 148 O4 BNAG E 1 30.115 44.862 -25.440 0.50104.91 EO HETATM 149 C5 BNAG E 1 29.907 42.532 -26.038 0.50 94.99 EC HETATM 150 C6 BNAG E 1 30.373 42.426 -27.500 0.50 86.60 EC HETATM 151 O6 BNAG E 1 29.320 42.743 -28.381 0.50 77.76 EO HETATM 152 O5 BNAG E 1 29.866 41.216 -25.458 0.50 99.19 EO ATOM745 N ASN A 116 27.207 36.475 -25.453 1.00 62.15 AN ATOM746 CA AASN A 116 28.475 37.144 -25.135 0.50 61.77 AC ATOM747 CB AASN A 116 28.182 38.336 -24.223 0.50 69.02 AC ATOM748 CG AASN A 116 29.037 39.555 -24.495 0.50 79.45 AC ATOM749 OD1AASN A 116 28.656 40.644 -24.047 0.50 83.18 AO ATOM750 ND2AASN A 116 30.178 39.419 -25.218 0.50 87.72 AN ATOM751 C ASN A 116 29.353 36.143 -24.389 1.00 53.28 AC ATOM752 O ASN A 116 29.778 36.380 -23.266 1.00 48.83 AO ATOM753 CA BASN A 116 28.575 37.144 -25.135 0.50 61.77 AC ATOM754 CB BASN A 116 28.282 38.336 -24.223 0.50 69.02 AC ATOM755 CG BASN A 116 29.487 39.201 -23.920 0.50 79.45 AC ATOM756 OD1BASN A 116 30.611 38.710 -24.084 0.50 83.18 AO ATOM757 ND2BASN A 116 29.299 40.471 -23.478 0.50 87.72 AN The Refmac log output shows that link description was recognized correctly for each conformation: WARNING : residue: NAG 1 chain:EE atom: "O1 " is absent in coord_file WARNING : link(spec):NAG-ASN is found dist = 1.466 ideal_dist= 1.439 ch:EE res: 1 NAG
[ccp4bb] Alternate sugar conformations in refmac 5.5.0110
Dear all, I am trying to refine a beta-D-N-Acetyl glucosamine moiety (NAG) linked to an asparagine (ASN) in Refmac. (version CCP4 6.3: Refmac_5.5.0110 version 5.5.0110 : 08/05/10) The sugar has two alternate conformations that occupy the same position in the electron density but are rotated 180° relative to each other. Even though I have defined two alternate conformations for the asparagine side chain, the sugar and the beta-link, Refmac pushes the two conformations apart, out of the electron density (while still honouring the link to Asn). So it seems that Refmac applies repulsive forces between the alternate conformations. Did anyone else experience this and/or can suggest a fix? All help is very much appreciated! My definitions for the alternate conformations in the PDB file are below: LINKRC1 ANAG E 1 ND2AASN A 116NAG-ASN LINKRC1 BNAG E 1 ND2BASN A 116NAG-ASN HETATM 125 C1 ANAG E 1 30.978 40.626 -25.446 0.50 98.96 EC HETATM 126 C2 ANAG E 1 30.428 41.897 -26.138 0.50100.81 EC HETATM 127 N2 ANAG E 1 29.783 41.751 -27.447 0.50 94.26 EN HETATM 128 C7 ANAG E 1 28.807 42.561 -27.924 0.50 89.45 EC HETATM 129 O7 ANAG E 1 28.325 42.377 -29.035 0.50 83.16 EO HETATM 130 C8 ANAG E 1 28.252 43.720 -27.128 0.50 87.63 EC HETATM 131 C3 ANAG E 1 31.618 42.847 -26.221 0.50102.77 EC HETATM 132 O3 ANAG E 1 31.420 43.888 -27.159 0.50102.25 EO HETATM 133 C4 ANAG E 1 31.840 43.369 -24.802 0.50103.37 EC HETATM 134 O4 ANAG E 1 32.969 44.217 -24.782 0.50104.91 EO HETATM 135 C5 ANAG E 1 32.040 42.223 -23.785 0.50 94.99 EC HETATM 136 C6 ANAG E 1 31.564 42.633 -22.381 0.50 86.60 EC HETATM 137 O6 ANAG E 1 32.632 42.591 -21.462 0.50 77.76 EO HETATM 138 O5 ANAG E 1 31.458 40.954 -24.130 0.50 99.19 EO HETATM 139 C1 BNAG E 1 30.271 40.925 -24.108 0.50 98.96 EC HETATM 140 C2 BNAG E 1 31.415 41.878 -23.684 0.50100.81 EC HETATM 141 N2 BNAG E 1 32.048 41.664 -22.378 0.50 94.26 EN HETATM 142 C7 BNAG E 1 33.331 41.981 -22.079 0.50 89.45 EC HETATM 143 O7 BNAG E 1 33.784 41.778 -20.959 0.50 83.16 EO HETATM 144 C8 BNAG E 1 34.276 42.586 -23.092 0.50 87.63 EC HETATM 145 C3 BNAG E 1 30.816 43.277 -23.775 0.50102.77 EC HETATM 146 O3 BNAG E 1 31.569 44.240 -23.061 0.50102.25 EO HETATM 147 C4 BNAG E 1 30.718 43.597 -25.266 0.50103.37 EC HETATM 148 O4 BNAG E 1 30.115 44.862 -25.440 0.50104.91 EO HETATM 149 C5 BNAG E 1 29.907 42.532 -26.038 0.50 94.99 EC HETATM 150 C6 BNAG E 1 30.373 42.426 -27.500 0.50 86.60 EC HETATM 151 O6 BNAG E 1 29.320 42.743 -28.381 0.50 77.76 EO HETATM 152 O5 BNAG E 1 29.866 41.216 -25.458 0.50 99.19 EO ATOM745 N ASN A 116 27.207 36.475 -25.453 1.00 62.15 AN ATOM746 CA AASN A 116 28.475 37.144 -25.135 0.50 61.77 AC ATOM747 CB AASN A 116 28.182 38.336 -24.223 0.50 69.02 AC ATOM748 CG AASN A 116 29.037 39.555 -24.495 0.50 79.45 AC ATOM749 OD1AASN A 116 28.656 40.644 -24.047 0.50 83.18 AO ATOM750 ND2AASN A 116 30.178 39.419 -25.218 0.50 87.72 AN ATOM751 C ASN A 116 29.353 36.143 -24.389 1.00 53.28 AC ATOM752 O ASN A 116 29.778 36.380 -23.266 1.00 48.83 AO ATOM753 CA BASN A 116 28.575 37.144 -25.135 0.50 61.77 AC ATOM754 CB BASN A 116 28.282 38.336 -24.223 0.50 69.02 AC ATOM755 CG BASN A 116 29.487 39.201 -23.920 0.50 79.45 AC ATOM756 OD1BASN A 116 30.611 38.710 -24.084 0.50 83.18 AO ATOM757 ND2BASN A 116 29.299 40.471 -23.478 0.50 87.72 AN The Refmac log output shows that link description was recognized correctly for each conformation: WARNING : residue: NAG 1 chain:EE atom: "O1 " is absent in coord_file WARNING : link(spec):NAG-ASN is found dist = 1.466 ideal_dist= 1.439 ch:EE res: 1 NAG at:C1 A->AA res: 116 ASN at:ND2 A WARNING : link(spec):NAG-ASN is found dist = 1.244 ideal_dist= 1.439 ch:EE res: 1 NAG at:C1 B->AA res: 116 ASN at:ND2 B Best regards, Markus -- Markus Meier, Ph.D. University of Manitoba Department of Chemistry 144 Dysart Road
Re: [ccp4bb] Program or server to predict Kd from complex structure
Hi Wei, I'm unsure if this will help, as i've never used it myself, but a former colleague in France is working on such a server? http://2p2idb.cnrs-mrs.fr/ But as everyone else has stated, only use this in comparison to some hard physical data. Cheers, Mat From: Ed. Pozharski To: CCP4BB@JISCMAIL.AC.UK Sent: Thursday, 18 April 2013, 8:46 Subject: Re: [ccp4bb] Program or server to predict Kd from complex structure Don't believe such program/server does exist. Notice that you are asking for something that *can* predict Kd. One can *try* making such predictions and they may even be routinely in the ballpark, assuming that you are satisfied with being routinely off by, say, an order of magnitude. One can easily predict general trends. For example, larger buried apolar surface will generally result in lower Kd. As for individual Kd prediction accuracy, that's another story. It's unknown to me what your goal is, but if you are trying to replace experimental Kd determination with a magic program, please don't. Cheers, Ed. Original message From: Wei Liu Date: 04/18/2013 4:39 AM (GMT-05:00) To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] Program or server to predict Kd from complex structure Dear all, Does anyone know a program or web server that can predict Kd value between two proteins from a solved complex structure? Regards Wei
Re: [ccp4bb] Difficult data
Hi, You also can try the MR program Queen of Spades (Qs) ( http://utopia.duth.gr/~glykos/Qs.html; documentation, http://utopia.duth.gr/~glykos/pdf/Qs.pdf). It is a multi-dimensional MR, so it will use a lot of CPU time and memory, but might be worth try it. Good luck. Andrey Nascimento 2013/4/18 > Stephen, > > Stephen, > > Although your peptide is smaller than the one I once worked on, here are > some thoughts that might be applicable. > > 1. Check and play with the radius of integration in the molecular > replacement. The default is probably not appropriate for your case but the > value should be much smaller than the default. > 2. Take a model - any model - of your peptide and make an arbitrary > artificial dataset by rotating the model around an arbitrary angle, and put > it in an arbitrary unit cell (say P1 for simplicity). Then use the original > non-rotated model and see what parameters will give you the best solution > and use those as starting parameters for your search. > 3. Consider that your model may be very asymmetric, i.e. much longer in > one direction than the other. In theory, you want the radius of integration > to be such that it covers one copy of the model but not more than one. If > the peptide is much longer than it is wide (which is somewhat likely), you > might run into the situation where the correct radius for the length would > incorporate multiple copies in the other direction(s). If this is the case, > I am not sure you can fix it. In my humble opinion, which might be very > out-of-date, this might be one of the reasons why MR does not work well on > small molecules. > 4. I think that it is possible that your crystal could be built from > multiple copies of randomly oriented copies of the peptide, which are > similar in their nature, but not exactly the same. This sounds odd but I > convinced myself a long time ago that such a crystal could be made. > > A long time ago I worked on a sea anemone toxin that had similar > properties. At the time I could not make step 2 above work, that is, I > convinced myself that I was unable to find parameters that did the job. > That was enough for my mentor to tell me that I should not pursue the > project... Of course such molecules are easily(*) resolved with NMR. > > Mark > (*) Relative statement, and not by me. > > > -Original Message- > From: Stephen Campbell > To: CCP4BB > Sent: Tue, Apr 16, 2013 7:39 pm > Subject: [ccp4bb] Difficult data > > Hello, > > I am having a few issues with a data set I have been working on recently, > and was hoping to get some ideas on how to deal with it, if anyone is in > the mood. > > I have been working with a very small bacterocin (about 3 kDa) and set up > some crystal trays in hope of getting some high diffracting crystals. I > failed, but did manage to get a data set of reasonable quality to about 4A > from crystals that reproduce very poorly. Now, this sounds horrendous, but > the MR model I have available is of a similar bacteriocin, whose structure > is predicted to be essentially identical (different ORF, but almost > identical sequence). I was thinking it would be done in a day. The > bravais lattice is P4, and 118 x 118 x 165 (which seems HUGE for such a > small protein...indeed calling it a protein is generous...peptide). The > data seems reasonably nice (nice spots, no visible overlap within 4A, but > is very mosaic, about 1.5 degrees. > > The data integrates and scales nicely, with very good chi2, R-factors and > % rejected reflections. It is hard to predict the correct space group, > since all the tetragonal options have the same stats. The systematic > absences seem to predict p41212 (as does pointless), but it wouldn't be the > first time I screwed that up. > > I can't get a solution, no matter what I try. Is this the nature of such > a small peptide in such a large unit cell (placing the first model is > difficult for MR since there may be many copies in the AU), or are there > some tricks? Is it likely that the unit cell is wrong? Self Rotation > functions give 8 peaks, but this is considering a peak fairly generously > (approx. 15-20% of origin). Are there some blatantly obvious red flags > that I may be missing? Any advice would be great - even if that advice is > that it may be time to move on. > > I should note that I have considered the idea that the peptide may be > forming some sort of oligomeric structure such as a coiled coil, but it > fails coiled coil predicting software, and there is no evidence that this > should be the case. The homologous structure is very rigid, and I would > say fairly confidently that mine is likely the same - I just want to > confirm it. > > Thanks so much, > > Stephen Campbell > Post Doctoral Fellow > Department of Biochemistry > McGill University >
Re: [ccp4bb] Neutrons and Life Sciences symposium 29-31 May Lund
Dear All, This is a final reminder to register for the Neutrons and Life Sciences meeting to be held in Lund on May 29-31. Deadline is tomorrow, Friday the 19th. Go-go-go :-) https://indico.esss.lu.se/indico/conferenceDisplay.py?confId=65 With the best regards, Bente From: Bente Vestergaard Sent: Thursday, March 21, 2013 1:20 PM To: ccp4bb@jiscmail.ac.uk Subject: Neutrons and Life Sciences symposium 29-31 May Lund Dear Colleagues, we are pleased to announce this meeting and invite you to submit abstracts until the 19th of April. Please print and post the attached conference flyer, and distribute further to any colleagues you think may be interested. Please see more below. Neutrons and Life Sciences May 29-31 2013, Lund, Sweden This ESS Science Symposium, co-hosted with the University of Copenhagen and the MoreLife Network at Lund University, will bring together current and potential users of neutron techniques in the biomedical sciences to discuss common challenges and future opportunities at ESS. The program will feature talks by prominent experts on a wide range of current high impact science in molecular biology and biomedical research as well as state-of-the art applications of neutron scattering techniques. Scope Biostructural research related to: molecular biology, biochemistry and biophysics, biotechnology and biomaterials, and biomedical research. Registration: 120 eur Abstract and registration deadline: 19th of April Confirmed Speakers Maikel Rheinstädter, McMaster University Yun Liu, NIST Center for Neutron Scattering Derek Logan, Lund University Jeremy Lakey, Newcastle University Ole Mouritsen, University of Southern Denmark Odense Tassos Perrakis, Netherlands Cancer Institute Giovanna Fragneto, Institut Lauge Langevin, Grenoble Olwyn Byron, Glasgow University The meeting will be held at the new Elite Hotel Ideon, Scheelevägen 27, Lund, Sweden. Registration and abstract submission are now open, for more information, please visit: https://indico.esss.lu.se/indico/conferenceDisplay.py?confId=65 Organising committee: Hanna Wacklin, ESS, Esko Oksanen, ESS, Sindra Petersson Årsköld, ESS, Lise Arleth, University of Copenhagen, Bente Vestergaard, University of Copenhagen, Marite Cardenas, University of Copenhagen, Jens Lagerstedt Lund University. Bente Vestergaard, Associate Professor, PhD BioSAXS - Biostructural Research Dept. Drug Design and Pharmacology University of Copenhagen Universitetsparken 2 DK-2100 Copenhagen Denmark bente.vesterga...@sund.ku.dk http://www.farma.ku.dk/staff/BV
Re: [ccp4bb] Program or server to predict Kd from complex structure
Don't believe such program/server does exist. Notice that you are asking for something that *can* predict Kd. One can *try* making such predictions and they may even be routinely in the ballpark, assuming that you are satisfied with being routinely off by, say, an order of magnitude. One can easily predict general trends. For example, larger buried apolar surface will generally result in lower Kd. As for individual Kd prediction accuracy, that's another story. It's unknown to me what your goal is, but if you are trying to replace experimental Kd determination with a magic program, please don't. Cheers, Ed. Original message From: Wei Liu Date: 04/18/2013 4:39 AM (GMT-05:00) To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] Program or server to predict Kd from complex structure Dear all, Does anyone know a program or web server that can predict Kd value between two proteins from a solved complex structure? Regards Wei
Re: [ccp4bb] Program or server to predict Kd from complex structure
For the low cost of $10 USD, this should be about as reliable :) http://www.amazon.com/Mattel-30188-Magic-8-Ball/dp/B1ZWV7 Not trying to be a curmudgeon, but this is a really hard problem! Steve -Original Message- From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Wei Liu Sent: Thursday, April 18, 2013 4:40 AM To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] Program or server to predict Kd from complex structure Dear all, Does anyone know a program or web server that can predict Kd value between two proteins from a solved complex structure? Regards Wei Notice: This e-mail message, together with any attachments, contains information of Merck & Co., Inc. (One Merck Drive, Whitehouse Station, New Jersey, USA 08889), and/or its affiliates Direct contact information for affiliates is available at http://www.merck.com/contact/contacts.html) that may be confidential, proprietary copyrighted and/or legally privileged. It is intended solely for the use of the individual or entity named on this message. If you are not the intended recipient, and have received this message in error, please notify us immediately by reply e-mail and then delete it from your system.
Re: [ccp4bb] Program or server to predict Kd from complex structure
Hi, As far as I understand the DeltaG given by PISA is kind of a "stability" measure of the complex, not its binding DeltaG. It is also based on a small part of the terms that contribute to a binding energy. I may be wrong about that, but in any case, predicting a KD from a single structure is something highly risky. The first thing you are leaving out is entropy, which may be the most important term. You can estimate it from normal modes analysis, but you would need to first minimize the energy of the structure. Molecular dynamics (MD) people use a method called MM-PBSA where they try to predict KDs from a number (hundreds or more) of structures extracted from an MD simulation. The method is more or less established, but the results are more meaningful in the context of comparisons than for the prediction of absolute binding energies. If you are only interested in some of the components of the binding energies, like electrostatic and apolar binding and polar/apolar solvation terms, you could use something like APBS (http://www.poissonboltzmann.org/apbs/) Cheers, Miguel Ortiz Lombardía Architecture et Fonction des Macromolécules Biologiques (UMR7257) CNRS, Aix-Marseille Université Case 932, 163 Avenue de Luminy, 13288 Marseille cedex 9, France Tel: +33(0) 491 82 55 93 Fax: +33(0) 491 26 67 20 mailto:miguel.ortiz-lombar...@afmb.univ-mrs.fr http://www.afmb.univ-mrs.fr/Miguel-Ortiz-Lombardia Le 18/04/13 11:34, Boaz Shaanan a écrit : > Hi, > > PISA have something like this, I think, or at least deltaG estimate. > > Boaz > > Boaz Shaanan, Ph.D. > Dept. of Life Sciences > Ben-Gurion University of the Negev > Beer-Sheva 84105 > Israel > > E-mail: bshaa...@bgu.ac.il > Phone: 972-8-647-2220 Skype: boaz.shaanan > Fax: 972-8-647-2992 or 972-8-646-1710 > > > > > > > From: CCP4 bulletin board [CCP4BB@JISCMAIL.AC.UK] on behalf of Wei Liu > [we...@me.com] > Sent: Thursday, April 18, 2013 11:39 AM > To: CCP4BB@JISCMAIL.AC.UK > Subject: [ccp4bb] Program or server to predict Kd from complex structure > > Dear all, > > Does anyone know a program or web server that can predict Kd value between > two proteins from a solved complex structure? > > Regards > Wei >
Re: [ccp4bb] Program or server to predict Kd from complex structure
Hi, PISA have something like this, I think, or at least deltaG estimate. Boaz Boaz Shaanan, Ph.D. Dept. of Life Sciences Ben-Gurion University of the Negev Beer-Sheva 84105 Israel E-mail: bshaa...@bgu.ac.il Phone: 972-8-647-2220 Skype: boaz.shaanan Fax: 972-8-647-2992 or 972-8-646-1710 From: CCP4 bulletin board [CCP4BB@JISCMAIL.AC.UK] on behalf of Wei Liu [we...@me.com] Sent: Thursday, April 18, 2013 11:39 AM To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] Program or server to predict Kd from complex structure Dear all, Does anyone know a program or web server that can predict Kd value between two proteins from a solved complex structure? Regards Wei
[ccp4bb] Program or server to predict Kd from complex structure
Dear all, Does anyone know a program or web server that can predict Kd value between two proteins from a solved complex structure? Regards Wei
