Histidine as a hydrogen bond acceptor in Phenix refine
Hi All, I've been refining a 1.1 Å structure with explicit hydrogen atoms and noticed that the serine HG atom (hydrogen atom attached to oxygen gamma) is rotated more than 90 degrees from the OG - NE2 (histidine) line (5 cases observed). In this position, the HG is staggered with the two carbon beta hydrogens and should be the preferred configuration. However, there is a histidine nearby with atom NE2 at 2.7 Å from the serine OG and in good geometry for Hbond formation. The other nitrogen, ND1, is protonated and interacting with an aspartic acid (similar to the catalytic triad configuration). In this protomer, the NE2 atom has a lone pair and should act as an acceptor. Thus, the OG - H - NE2 angle should be as close to 180 as possible for an ideal hydrogen bond angle. The OG - H - NE2 angle of more than 90 degrees looks a little off to me. I checked the other program, e.g. Schrodinger Prime to see how it treats this situation and found that all the OG - H - NE2 angles are within 10-60 degrees from the ideal value of 180, certainly not 90 as observed in Phenix refine. My question is is NE2 or ND1 atom of the HID or HIE protomer treated as a potential hydrogen bond acceptor in Phenix? For other acceptors like the backbone carbonyl oxygen, carboxylic acid oxygen, and water oxygen, the hydrogen bond angle OG -H -O looks good. Not when it involves histidine atom NE2 or ND1 though. The pH of the crystallization is 7 by the way. Also, there's no water nearby that would draw the HG away from the histidine. Jason
Hi Jason, it is somewhat uneasy for me to translate this story into a picture that I could analyze and draw conclusions.. So could you please send me the inputs and outputs of phenix.refine and tell what residue (chain id and residue id) that is not behaving well. Also, if you send me the output of PrimeX (or any other file that you think has correct positions of all atoms in question) - that would be very helpful. Please send files to my email directly, not the entire mailing list! Thanks, Pavel On 9/25/14 10:41 AM, Phan, Jason wrote:
Hi All,
I've been refining a 1.1 Å structure with explicit hydrogen atoms and noticed that the serine HG atom (hydrogen atom attached to oxygen gamma) is rotated more than 90 degrees from the OG - NE2 (histidine) line (5 cases observed). In this position, the HG is staggered with the two carbon beta hydrogens and should be the preferred configuration. However, there is a histidine nearby with atom NE2 at 2.7 Å from the serine OG and in good geometry for Hbond formation. The other nitrogen, ND1, is protonated and interacting with an aspartic acid (similar to the catalytic triad configuration). In this protomer, the NE2 atom has a lone pair and should act as an acceptor. Thus, the OG - H - NE2 angle should be as close to 180 as possible for an ideal hydrogen bond angle. The OG - H - NE2 angle of more than 90 degrees looks a little off to me. I checked the other program, e.g. Schrodinger Prime to see how it treats this situation and found that all the OG - H - NE2 angles are within 10-60 degrees from the ideal value of 180, certainly not 90 as observed in Phenix refine. My question is is NE2 or ND1 atom of the HID or HIE protomer treated as a potential hydrogen bond acceptor in Phenix? For other acceptors like the backbone carbonyl oxygen, carboxylic acid oxygen, and water oxygen, the hydrogen bond angle OG -H -O looks good. Not when it involves histidine atom NE2 or ND1 though. The pH of the crystallization is 7 by the way. Also, there's no water nearby that would draw the HG away from the histidine.
Jason _______________________________________________ phenixbb mailing list [email protected] http://phenix-online.org/mailman/listinfo/phenixbb
Hi Jason, out of curiosity: By 'explicit hydrogen atoms' do you mean that you refine the hydrogen parameters rather than using the riding hydrogen model? This is very bold for even at and beyond Acta C resolution limits (0.8A) one usually only uses the riding atom model for hydrogens. Best, Tim On 09/25/2014 07:41 PM, Phan, Jason wrote:
Hi All,
I've been refining a 1.1 Å structure with explicit hydrogen atoms and noticed that the serine HG atom (hydrogen atom attached to oxygen gamma) is rotated more than 90 degrees from the OG - NE2 (histidine) line (5 cases observed). In this position, the HG is staggered with the two carbon beta hydrogens and should be the preferred configuration. However, there is a histidine nearby with atom NE2 at 2.7 Å from the serine OG and in good geometry for Hbond formation. The other nitrogen, ND1, is protonated and interacting with an aspartic acid (similar to the catalytic triad configuration). In this protomer, the NE2 atom has a lone pair and should act as an acceptor. Thus, the OG - H - NE2 angle should be as close to 180 as possible for an ideal hydrogen bond angle. The OG - H - NE2 angle of more than 90 degrees looks a little off to me. I checked the other program, e.g. Schrodinger Prime to see how it treats this situation and found that all the OG - H - NE2 angles are within 10-60 degre es from the ideal value of 180, certainly not 90 as observed in Phenix refine. My question is is NE2 or ND1 atom of the HID or HIE protomer treated as a potential hydrogen bond acceptor in Phenix? For other acceptors like the backbone carbonyl oxygen, carboxylic acid oxygen, and water oxygen, the hydrogen bond angle OG -H -O looks good. Not when it involves histidine atom NE2 or ND1 though. The pH of the crystallization is 7 by the way. Also, there's no water nearby that would draw the HG away from the histidine.
Jason _______________________________________________ phenixbb mailing list [email protected] http://phenix-online.org/mailman/listinfo/phenixbb
-- Dr Tim Gruene Institut fuer anorganische Chemie Tammannstr. 4 D-37077 Goettingen GPG Key ID = A46BEE1A
On Fri, Sep 26, 2014 at 1:16 AM, Tim Gruene
out of curiosity: By 'explicit hydrogen atoms' do you mean that you refine the hydrogen parameters rather than using the riding hydrogen model? This is very bold for even at and beyond Acta C resolution limits (0.8A) one usually only uses the riding atom model for hydrogens.
+1 Jason, I think you may be misunderstanding how hydrogens are handled internally. The geometry restraints used in Phenix (and Refmac, etc.) are based on the assumption that the data guide the atoms reasonably well, and do not include any attractive forces or explicit hydrogen-bonding. Reduce will take hydrogen bonding into account when it adds hydrogens to the model, but that's it - and I'm not sure how well this will handle hydroxyl hydrogens. -Nat
Thanks, Tim & Nate. I'm using the riding model as implemented. I grabbed this catalytic triad pic from Wikimedia which is very similar to what I have. What I was trying to say is in my phenix refinement, the Ser-O-H----NE2-His angle is greater than 90 degrees. The serine O-H bond is projected perpendicularly to the O----N imaginary straight line, instead of pointing along that line or say 0-60 degrees off of it, which is a stronger hydrogen bonding angle than say 90 or greater. Nate made a good point but like I said, if the acceptor is an oxygen be it from the back bone, side chain or water, the hydroxyl hydrogen would "point" at it at an angle close to 180, a straight line, as seen in this picture. But when you have a histidine NE2 and not an oxygen, the hydroxyl O-H bond would rotate more than 90 degrees relative to that straight line. That made me think that Phenix does model hydrogen bonding interactions, just maybe not as consistently. I'll send Pavel the Phenix refined and the Primex refined models as requested.
[http://upload.wikimedia.org/wikipedia/commons/4/41/Catalytic_triad.png]
On Sep 26, 2014, at 4:59 AM, Nathaniel Echols wrote:
On Fri, Sep 26, 2014 at 1:16 AM, Tim Gruene
On Fri, Sep 26, 2014 at 8:42 AM, Phan, Jason
That made me think that Phenix does model hydrogen bonding interactions, just maybe not as consistently.
If this is happening it's entirely due to the way Reduce adds hydrogens - the actual minimization in phenix.refine won't do anything special. -Nat
participants (4)
-
Nathaniel Echols -
Pavel Afonine -
Phan, Jason -
Tim Gruene