PROPOSED WORK November 24, 2010 cc. Chun, YunKyong, Dirk, Ardyth, and Fred (iit) Attachments PNPRepulsion20100809_2_Communications in Mathematical Sciences accepted.pdf (application/pdf) 228K Energetics of Divalent Selectivity RyR with Supplement Feb 2008.pdf (application/pdf) 1299K Dirk Gillespie CV March 2010.pdf (application/pdf) 157K Dear Xiaofan, Shuwang, and Jinquiao Thank you for coffee, lunch, coffee, and a fine conversation! I think the next step is to make a specific calculation. I would suggest we try to calculate the current voltage relations in the Supplemental Material of the paper by Dirk Gillespie (attached). [Gillespie, D., Energetics of divalent selectivity in a calcium channel: the ryanodine receptor case study. Biophys J, 2008. 94(4): p. 1169-84.] The figures we will reproduce are Figures S1-S8. I include Dirk's entire paper, but the Supplemental Material is our goal. Dirk is eager to help with this work. He will kindly provide us all the details of the structure etc. Those are also available in the publication to which the Supplement is attached. The work should include Chun Liu and YunKyong Hyon as collaborators. We can extend what they have done and do not worry, there is plenty for all of us to do. (Remember there are many channel types of great interest with many phenomena to study. These reach well beyond the current voltage curves of Dirk's papers. I attach a CV of Dirk so you can see the sort of thing he has done on the RyR. This is only a small part of what can and should be done on other channels. My collaborators and I have done a great deal on the calcium and sodium channels of heart and skeletal muscle and nerve fibers. There are literally tens of other channel types with equivalent data sets that need to be analyzed.). We will use PNP-finite size to calculate these IV curves, as specified in the paper attached "A mathematical model for the hard sphere repulsion in ionic solutions" [Hyon, Y.; Eisenberg, B.; Liu, C. Communications in Mathematical Sciences (in the press) ]. We may slightly modify the model to deal with the interface with the bath. YunKyong, Chun, and I have completed and submitted a paper on that modification and will be happy to discuss it with you as we proceed. It simplifies the work of the paper attached and does NOT add to the numerical burden. Indeed, it was designed to reduce that burden. We will calculate current as a function of time as a solution of equations 3.17 and 3.18 of the attached Hyon et al paper. The solution satisfies the energy variational principle 3.19. The steady state value will be plotted vs. voltage and that will be compared with Dirk's calculation. This paper will provide the preliminary data necessary to support a series of NIH, NSF, and combined NIH/NSF grant applications to use PNP-finite size as a model of a range of properties of the RyR and then other channels. Unfortunately, there is no point applying until after we have shown we can do these calculations. Once the software is written, we should put in the form of a web accessible package, write an SBIR grant for it, and make it commercially available (at low cost to students, moderate cost to researchers, and reasonable cost to everyone else). My wife Ardyth Eisenberg is an attorney who has experience setting up companies for STTR's or SBIR's, and submitting such grants. She does not charge for this work, unless the grant is awarded. The fees saved are considerable. I hope this provides you food for thought, to go along with the food for Thanksgiving. This is an enormous professional opportunity; We can be the first to exploit Chun's breakthrough, and YunKyong's wonderful numerical work to deal with a real data set. We are fortunate that Chun, YunKyong, and Dirk are so eager to help and that Ardyth will make it possible to create a commercial outfit and help it submit grants. As ever Bob PS In interdiciplinary work like this, the chances of confusion are very great. It is important that JUST AS SOON as a question arises, it gets answered. If there is ANYTHING that is confusing in what I have written, it means I have written it badly. Just ask!! Then I will try to fix the confusion before it metastasizes into a waste of your time. ======================== Return Address for email: beisenbe@rush.edu Bob aka RS Eisenberg Bard Endowed Professor and Chairman Dept of Molecular Biophysics & Physiology Rush University 1653 West Congress Parkway Chicago IL 60612 USA Office Location: Room 1291 of Jelke Building at 1750 West Harrison Email: beisenbe@rush.edu Voice: +312-942-6467 FAX: +312-942-8711 FAX to Email: +801-504-8665 Department WebSite: http://www.phys.rush.edu/Personal WebSite: http://www.phys.rush.edu/RSEisenberg/ ====================================