[Demelerlab] updates to the UltraScan SOMO residue definitions

Tue Jul 25 15:43:05 MDT 2023

Hi Borries,

I am going to be in Italy for the first two weeks in August. I might have some free time to Zoom during the first week, but I think it best if you not schedule the meeting around me.

Best,
James

> On Jul 25, 2023, at 8:10 AM, Borries Demeler <demeler at gmail.com> wrote:
> 
> Hello James and Jason,
> would you like to be involved in the development and testing of a program that can build beadmodels from arbitrary residues in molecular structures and predict their PSVs? Mattia is in Italy, which is +9 hours, so this may limit available time for conference calls, but maybe either Mattia is available in the evening or you guys don't mind getting up early ;)
> Let me know if you want to be involved and I will schedule a meeting.
> -Borries
> 
> On Mon, Jul 24, 2023 at 1:33 PM Mattia Rocco <mattia.rocco at quipo.it <mailto:mattia.rocco at quipo.it>> wrote:
>> Hi Bo - excellent! :-) From my previous interactions with Saeed, I believe he would be an excellent fit for the job, with help/assistance from the other people already involved! Let's set up that meeting at a time of your convenience. Me, except for Fridays, I'm usually pretty much available... ;-)
>> 
>> Best - Mattia
>> 
>> Il 2023-07-24 18:26 Borries Demeler ha scritto:
>> 
>>> Hi Mattia,
>>> thanks so much for doing this. I would be very interested in having a program for not only predicting the bead models for different groups, but also the vbar calculations in an automated way. James Nowick has already used Helmut Durchschlag's paper to predict PSV for various amyloid peptide mimics, and has experience on how to use this program. Saeed in our group is a MD molecular modeling expert as well as an expert UltraScan programmer, I am thinking he would be perfect to develop such a module for UltraScan. But we would need some scientific help on how to develop the algorithm, if you and Emre could assist on this end then we could use some of the delta-linked ornithin residues as examples, since James has already worked them out for the PSV.
>>>  
>>> We may need a Zoom call with you and Emre at some point to get us started with the envisioned program.
>>>  
>>> Thanks very much, -Borries
>>> 
>>> On Mon, Jul 24, 2023 at 2:11 AM Mattia Rocco <mattia.rocco at quipo.it <mailto:mattia.rocco at quipo.it>> wrote:
>>> Dear Bo,
>>> 
>>> apologies, I totally forgot of your request last week, when I returned to Genova. While I will now have a look at it, I seize this occasion to inquire with you if you would be keen to approach this issue from a programming side. That is, develop a way of semi-automatically code, with just an user supervision, for non-coded residues in US-SOMO. I would suggest to first start with the most important part, the calculation of the psv, which would also be very welcomed by the SAXS community. After all, Durchschlag & Zipper great work should be amenable to be coded in a program, relieving scientists from a demanding "manual" work.
>>> 
>>> For instance, would be the person that did calculate the psv for your unnatural amino-acids be willing to explore such a project? We could set-up a Zoom meeting to discuss strategies and potential implementations... I believe that a coding developed for the psv calculation would have many of the features needed to also code a new residue for US-SOMO. After all, it is likely that I would quit offering such a service in a not-too-distant future... ;-)
>>> 
>>> All the best - Mattia
>>> 
>>> 
>>> 
>>> Il 2023-07-09 23:52 Borries Demeler ha scritto:
>>> 
>>> Hi Mattia and Emre:
>>> We are working with the Nowick group from UCalifornia, Irvine, to study synthetic amyloid peptide mimics which include several non-canonical amino acids. Loading Xray and NMR generated PDBs into SOMO causes several errors due to these discrepancies:
>>>  
>>> Encountered the following warnings with your PDB structure:
>>> Chain B Molecule 1 Residue ORN 1: Non-coded residue. 
>>> Chain B Molecule 1 Residue PHI 5: Non-coded residue. 
>>> Chain B Molecule 1 Residue ORN 9: Non-coded residue. 
>>> Chain B Molecule 1 Residue SAR 13: Non-coded residue.
>>>  
>>> ...and various downstream issues with chain breaks resulting from these unknown residues. I suspect that due to the small size of these peptides we want to be as accurate as possible to represent the residues correctly, since they are likely extending into the solvent interface. Of great interest in amyloid research is the structure & function of small soluble oligomers, so this is what we are trying to investigate by AUC, NMR and X-ray, and being able to simulate expected oligomers by US-SOMO would be a great plus.
>>>  
>>> Can you please update the residue definition list for US-SOMO so these AAs are properly recognized? I think this would be a great and novel use of US-SOMO!
>>>  
>>> I have attached a number of PDB files from oligomeric structures of one of these peptides derived from NMR and Xray that were generated by Jason Zhu (Cc'ed) from James Nowick's lab, and since I am no expert in PDB formats, perhaps you and Jason can collaborate to get the residues added, and allow us to load them correctly?
>>>  
>>> We would be happy to include you in the manuscript author list for your help with the simulation. The s, D and frictional ratios would be directly compared with AUC data. Also, James has already worked out the partial specific volumes for these non-canonical amino acids using Helmut Durchschlag's papers. He can provide you with these values.
>>>  
>>> Thanks so much, -Borries
>>>  

James S. Nowick
Distinguished Professor
Department of Chemistry & Department of Pharmaceutical Sciences

Department of Chemistry
4126 Natural Sciences 1
University of California, Irvine
Irvine, CA 92697-2025

Phone:  (949)  824-6091
e-mail: jsnowick at uci.edu
Faculty Web Page: http://tinyurl.com/jsnowick/
Research Group Web Page: http://tinyurl.com/nowickgroup/
Pronouns: he/him/his

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