energy minimization
Dear I am trying to minimize a structure with HEME cofactor. I added heme frcmod and prep files from Amber parameter database in parm and prep folders respectively.I minimized the structure at different steps of steepest descent from 100 to 1000.But in all the structures FE of heme is not well aligned with HEME structure (it is pointed out of structure).I tried with both all atom and united atom frcmod and prep files but the results are same.Please find attached the minimized structure. Kindly tell me where am I wrong. Any help would be appreciated. Thank you Regards Sara
Hi Sara, There are a couple of problems here. One is that the heme coordinates / bond lengths aren’t very good, so Chimera’s estimates for the atom types is wrong for some of the atoms. The other problem is that because the iron is displaced out of the porphyrin ring, addh is adding hydrogens to the inside of the ring that would normally be prevented by the presence of the iron. Those hydrogens repel the iron of course. So, to correct things, you need to: 1) Delete all hydrogens 2) Correct the atom types 3) Add the hydrogens back 4) Delete inward-facing porphyrin-ring hydrogens 5) Add charges 6) Minimize The commands (Favorites→Command Line) corresponding to those steps are: 1) “del H” 2) “defattr /path/to/heme.defattr raise false” (I have attached the heme.defattr file) 3) “addh” 4) “del :hem@hd” 5) “addch” (this will take awhile with AM1-BCC charges) 6) Minimize however you were doing it before. I have also attached a session with all the above steps performed. The iron is not yet planar with the ring, but additional minimization will undoubtedly get it there. —Eric Eric Pettersen UCSF Computer Graphics Lab
On Jul 15, 2019, at 6:23 AM, sara20@mail.ustc.edu.cn wrote:
Dear I am trying to minimize a structure with HEME cofactor. I added heme frcmod and prep files from Amber parameter database in parm and prep folders respectively.I minimized the structure at different steps of steepest descent from 100 to 1000.But in all the structures FE of heme is not well aligned with HEME structure (it is pointed out of structure).I tried with both all atom and united atom frcmod and prep files but the results are same.Please find attached the minimized structure. Kindly tell me where am I wrong. Any help would be appreciated. Thank you
Regards Sara <min1Refined_model7.pdb>_______________________________________________ Chimera-users mailing list: Chimera-users@cgl.ucsf.edu Manage subscription: http://plato.cgl.ucsf.edu/mailman/listinfo/chimera-users
Hi Eric Thanks for your suggestions. I tried the mentioned steps but still facing the same issue (see attached file). I forgot to mention that I am minimizing the modelled structure, maybe that's why it's creating this problem. In modelling I modelled the structure with heme and also with out heme (and later on pasted the heme coordinates from template to model structure). I minimized both structures and ended up with the same problem. I am not sure where am I making mistake. I'd be grateful if you could guide me more. Regards Sara -----Original Messages----- From:"Eric Pettersen" <pett@cgl.ucsf.edu> Sent Time:2019-07-16 06:55:59 (Tuesday) To: sara20@mail.ustc.edu.cn Cc: "chimera-users@cgl.ucsf.edu BB" <chimera-users@cgl.ucsf.edu> Subject: Re: [Chimera-users] energy minimization Hi Sara, There are a couple of problems here. One is that the heme coordinates / bond lengths aren’t very good, so Chimera’s estimates for the atom types is wrong for some of the atoms. The other problem is that because the iron is displaced out of the porphyrin ring, addh is adding hydrogens to the inside of the ring that would normally be prevented by the presence of the iron. Those hydrogens repel the iron of course. So, to correct things, you need to: 1) Delete all hydrogens 2) Correct the atom types 3) Add the hydrogens back 4) Delete inward-facing porphyrin-ring hydrogens 5) Add charges 6) Minimize The commands (Favorites→Command Line) corresponding to those steps are: 1) “del H” 2) “defattr /path/to/heme.defattr raise false” (I have attached the heme.defattr file) 3) “addh” 4) “del :hem@hd” 5) “addch” (this will take awhile with AM1-BCC charges) 6) Minimize however you were doing it before. I have also attached a session with all the above steps performed. The iron is not yet planar with the ring, but additional minimization will undoubtedly get it there. —Eric Eric Pettersen UCSF Computer Graphics Lab
It turns out that without a cofactor stabilizing the position of the iron, the ff14SB force field parameters are such that the iron will minimize to be somewhat non-planar with the porphyrin ring. For instance if I take the 2j0p structure and delete everything but the heme and then run 1000 steps of steepest descent, the iron moves out of the plane of the ring. The OPLS force field has explicit parameters for maintaining the ring planarity of the iron, but that is beyond the scope of Chimera. You would have to run Amber of some other package yourself. —Eric
On Jul 15, 2019, at 8:44 PM, sara20@mail.ustc.edu.cn wrote:
Hi Eric Thanks for your suggestions. I tried the mentioned steps but still facing the same issue (see attached file). I forgot to mention that I am minimizing the modelled structure, maybe that's why it's creating this problem. In modelling I modelled the structure with heme and also with out heme (and later on pasted the heme coordinates from template to model structure). I minimized both structures and ended up with the same problem. I am not sure where am I making mistake. I'd be grateful if you could guide me more. Regards Sara
-----Original Messages----- From:"Eric Pettersen" <pett@cgl.ucsf.edu <mailto:pett@cgl.ucsf.edu>> Sent Time:2019-07-16 06:55:59 (Tuesday) To: sara20@mail.ustc.edu.cn <mailto:sara20@mail.ustc.edu.cn> Cc: "chimera-users@cgl.ucsf.edu <mailto:chimera-users@cgl.ucsf.edu> BB" <chimera-users@cgl.ucsf.edu <mailto:chimera-users@cgl.ucsf.edu>> Subject: Re: [Chimera-users] energy minimization
Hi Sara, There are a couple of problems here. One is that the heme coordinates / bond lengths aren’t very good, so Chimera’s estimates for the atom types is wrong for some of the atoms. The other problem is that because the iron is displaced out of the porphyrin ring, addh is adding hydrogens to the inside of the ring that would normally be prevented by the presence of the iron. Those hydrogens repel the iron of course. So, to correct things, you need to:
1) Delete all hydrogens 2) Correct the atom types 3) Add the hydrogens back 4) Delete inward-facing porphyrin-ring hydrogens 5) Add charges 6) Minimize
The commands (Favorites→Command Line) corresponding to those steps are:
1) “del H” 2) “defattr /path/to/heme.defattr raise false” (I have attached the heme.defattr file) 3) “addh” 4) “del :hem@hd” 5) “addch” (this will take awhile with AM1-BCC charges) 6) Minimize however you were doing it before.
I have also attached a session with all the above steps performed. The iron is not yet planar with the ring, but additional minimization will undoubtedly get it there.
—Eric
Eric Pettersen UCSF Computer Graphics Lab
<minnewRefined_model7.pdb>_______________________________________________ Chimera-users mailing list: Chimera-users@cgl.ucsf.edu <mailto:Chimera-users@cgl.ucsf.edu> Manage subscription: http://plato.cgl.ucsf.edu/mailman/listinfo/chimera-users <http://plato.cgl.ucsf.edu/mailman/listinfo/chimera-users>
participants (2)
-
Eric Pettersen -
sara20＠mail.ustc.edu.cn