From owner-chemistry@ccl.net Sat Dec 11 01:30:00 2010 From: "Kalju Kahn kalju**chem.ucsb.edu" To: CCL Subject: CCL: temperature and free rotation Message-Id: <-43337-101211012903-22491-FODmIU5Hak10QmcKSfHBig*server.ccl.net> X-Original-From: "Kalju Kahn" Content-Transfer-Encoding: 8bit Content-Type: text/plain;charset=iso-8859-1 Date: Fri, 10 Dec 2010 22:28:55 -0800 MIME-Version: 1.0 Sent to CCL by: "Kalju Kahn" [kalju%a%chem.ucsb.edu] Hallo Toomas! You are correct that kinetics is the ultimate answer here. Starting with Eyring equation, you can derive a predictive relationship that relates the critical free energy barrier to temperature once you agree on what "stable" means. If you define "stable" as having half-life of 24 hr, then the critical activation barrier at room temperature is about 100 kJ/mol. The approximate linear relationships between temperature and the critical activation barrier are: dG(kJ/mol) = 102 + 0.351(temp(C) - 25) for irreversible A --> B dG(kJ/mol) = 104 + 0.356(temp(C) - 25) for reversible A <-> B You can look at the derivations and details at: http://www.chem.ucsb.edu/~kalju/chem111/public/Stable_Conformer.pdf This could make an interesting exam question for next time I teach kinetics. Too bad we just had the final today! Parimate tervitustega Santa Barbarast, Kalju > > Sent to CCL by: Toomas Tamm [tt-ccl2~!~yki.ttu.ee] > Hello, > > I have been unable to find a clear answer to the following problem: > > Suppose we have calculated the energy profile of rotation about a given > single bond in a molecule. Given this data, I would like to know if the > conformers freely interconvert into each other (ie the molecule can > cross the rotational barrier) at a given temperature T. > > My original thought was to compare the barrier height with the energy > available in a vibrational mode, 1/2 kT. However, this leads to the > result that most methyl groups (barriers 2-3 kcal/mol) should not rotate > at room temperature (1/2 kT x N_A = 1/2 RT = 0.297 kcal/mol at 298K), > which contradicts common chemical knowledge. > > I understand that eventually we get to the kinetics aspect of the > problem (how rapid is the interconversion rate of conformers), but I > would rather like to have a general "rule of thumb" which could be used > for quick estimates. Which value do I need to compare the barrier height > with? > > -- > Toomas Tamm e-mail: tt-ccl2 (at) kky . ttu > . ee > Chair of Inorganic Chemistry voice: INT+372-620-2810 > Tallinn University of Technology fax: INT+372-620-2828 > Ehitajate tee 5, EE-19086 Tallinn, Estonia http://www.kk.ttu.ee/toomas/> > > ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Dr. Kalju Kahn Department of Chemistry and Biochemistry UC Santa Barbara, CA 93106 From owner-chemistry@ccl.net Sat Dec 11 02:44:00 2010 From: "Jean Jules FIFEN julesfifen++gmail.com" To: CCL Subject: CCL:G: Relaxed surface scan with frequencies at each point Message-Id: <-43338-101211023557-15994-+4gZDyeX03a93fLVFd5IAQ:+:server.ccl.net> X-Original-From: Jean Jules FIFEN Content-Type: multipart/alternative; boundary=90e6ba4fc2f016420004971d84d8 Date: Sat, 11 Dec 2010 08:35:32 +0100 MIME-Version: 1.0 Sent to CCL by: Jean Jules FIFEN [julesfifen\a/gmail.com] --90e6ba4fc2f016420004971d84d8 Content-Type: text/plain; charset=ISO-8859-1 The keywords to use are: *opt=modredundant freq. *Obviously, don't forget to specify coordinates which should be scanned as it would be done in a rigid scan. For further explanations, read gaussian manual. J. Jules. On 10 December 2010 22:37, J Bredenbeck jbreden[#]gmx.de < owner-chemistry%%ccl.net> wrote: > > Sent to CCL by: "J Bredenbeck" [jbreden!=!gmx.de] > Dear CCL Users, > > I would like to do a relaxed surface scan in Gaussian03 with a normal mode > calculation at each point after optimization. I would be great if somebody > could tell me how this type of calculation can be set up. > > Regards, > Jens> > > -- J. Jules. --90e6ba4fc2f016420004971d84d8 Content-Type: text/html; charset=ISO-8859-1 Content-Transfer-Encoding: quoted-printable
The keywords to use are: opt=3Dmodredundant freq. O= bviously, don't forget to=A0 specify coordinates which should be scanne= d as it would be done in a rigid scan. For further explanations, read gauss= ian manual.

J. Jules.

On 10 December 2010 22:37, = J Bredenbeck jbreden[#]gmx.de <owner-chemistry%%ccl.net> wrote:

Sent to CCL by: "J =A0Bredenbeck" [jbreden!=3D!gmx.de]
Dear CCL Users,

I would like to do a relaxed surface scan in Gaussian03 with a normal mode = calculation at each point after optimization. I would be great if somebody = could tell me how this type of calculation can be set up.

Regards,
Jens



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--90e6ba4fc2f016420004971d84d8-- From owner-chemistry@ccl.net Sat Dec 11 12:47:00 2010 From: "Deepangi Pandit deepangi.pandit~!~gmail.com" To: CCL Subject: CCL: Prediction & Identification of protein-ligand binding sites Message-Id: <-43339-101211124524-27671-+tXcGZKh7cLp/NhuYTQEPQ..server.ccl.net> X-Original-From: Deepangi Pandit Content-Type: text/plain; charset=ISO-8859-1 Date: Sat, 11 Dec 2010 12:44:32 -0500 MIME-Version: 1.0 Sent to CCL by: Deepangi Pandit [deepangi.pandit(!)gmail.com] Dear All: I tried to search literature and Internet to find a reliable method that I can use to identify protein-ligand binding site. I came across number of papers but I am unable to evaluate the methods before I start using them. I was also unable to find a review which compares the methods. It seems method can be broadly classified as "Geometry based" and "Energy Based". Could you please recommend from your own experience which method gives reasonable results. Also, feel free to share pros and cons of the method. Thank you. Deepa List of methods I came across Q-Site Finder http://www.bioinformatics.leeds.ac.uk/qsitefinder Surface triplet propensities http://opus.bch.ed.ac.uk/stp Screen http://interface.bioc.columbia.edu/screen From owner-chemistry@ccl.net Sat Dec 11 16:52:01 2010 From: "Peter Schmidtke pschmidtke[-]mmb.pcb.ub.es" To: CCL Subject: CCL: Prediction & Identification of protein-ligand binding sites Message-Id: <-43340-101211164728-23584-i8B95ybVcWd4sX7+ogk/5w|server.ccl.net> X-Original-From: Peter Schmidtke Content-Transfer-Encoding: 8bit Content-Type: text/plain; charset=ISO-8859-1 Date: Sat, 11 Dec 2010 22:45:54 +0100 MIME-Version: 1.0 Sent to CCL by: Peter Schmidtke [pschmidtke[*]mmb.pcb.ub.es] Dear Deepangi, protein-ligand binding site detection is a very active field and there is a large variety of methods out there. Since the publication of PocketPicker (http://www.journal.chemistrycentral.com/content/1/1/7/abstract/) lots of newer methods used the comparative table that was published with PocketPicker (table 2). A very recent example is the paper by Andrea Volkamer, where you have an update of this table with a few more recent methods (http://pubs.acs.org/doi/full/10.1021/ci100241y). This comparison is definitely arguable, but at least it gives some hint on general pocket prediction performance. In order to find the perfect method for your purpose you should maybe clarify what is the functionality your are seeking. There are lots of webservers out there, methods you have to pay and also free methods. Some questions that could influence your choice : 1 : Do you want to apply this method on a database of proteins or just a few structures? 2 : Do you want to identify putative drug binding sites or whatever binding site a method could find (general purpose pocket prediction) 3 : Do you want to find conserved pockets among homologs? Concerning question 1, if you just need a method for a few structures you can go for slower programs (mostly energy based algorithms) like SiteMap from Schrödinger (but you need a license) Q-SiteFinder or PocketPicker or Vice (I think it's sold by Tripos) There are surely more than that. If you need to process a large number of structures, considering geometry based methods might become an interesting choice. Choices could be Ligsite, fpocket, PASS, SiteFinder (included in MOE by CCG) ... Regarding question 2. Pocket prediction is not equal drug binding site prediction. Recent druggability prediction methods have been published and some scores are available ready for use in SiteMap (I don't know if you still have to calculate it or if they finally included it into the SiteMap distribution) and fpocket. I suspect also QSiteFinder might give indications on druggability (I extrapolate from the methodology I just read very quickly, so maybe I'm wrong here ;) ). Regarding question 3, I think ligsite csc can help there (http://projects.biotec.tu-dresden.de/pocket/), or else hpocket, which is part of the fpocket webserver : http://bioserv.rpbs.univ-paris-diderot.fr/fpocket/ I hope that this gives you at least a direction, there are really lots of methods and it is indeed not easy to know which one to use ;) Ah, I nearly forgot, metapocket2.0 is a sort of consensus pocket prediction method that makes use of LIGSITEcsc, PASS, Q-SiteFinder, SURFNET, Fpocket, GHECOM and ConCavity. This has again advantages and disadvantages, but well, at least you know that it exists ;) Good luck. Peter Schmidtke On 12/11/2010 06:44 PM, Deepangi Pandit deepangi.pandit~!~gmail.com wrote: > Sent to CCL by: Deepangi Pandit [deepangi.pandit(!)gmail.com] > Dear All: > I tried to search literature and Internet to find a reliable method > that I can use to identify protein-ligand binding site. I came across > number of papers but I am unable to evaluate the methods before I > start using them. I was also unable to find a review which compares > the methods. It seems method can be broadly classified as "Geometry > based" and "Energy Based". Could you please recommend from your own > experience which method gives reasonable results. Also, feel free to > share pros and cons of the method. > > Thank you. > Deepa > > List of methods I came across > > Q-Site Finder > http://www.bioinformatics.leeds.ac.uk/qsitefinder > > Surface triplet propensities > http://opus.bch.ed.ac.uk/stp > > Screen > http://interface.bioc.columbia.edu/screen> > >