From bio320@cvx12.inet.dkfz-heidelberg.de Mon Jan 11 14:53:51 1993 Date: Mon, 11 Jan 1993 13:53:51 +0100 From: Friedrich Rippmann Message-Id: <199301111253.AA26018@cvx12.inet.dkfz-heidelberg.de> To: CHEMISTRY@ccl.net Subject: summary: energy contribution of hbonds Some time ago I put this question to the net: >>>>Original posting<<<< I try to find some references for an apparently simple problem: What is the free energy contribution of an hbond (eg. of a peptide inhibitor in a protease)? I know that there is considerable dispute in the literature about the energy contribution, but I can't find appropriate references. What I would like to do is to correlate qualitatively a difference in binding energy with the ratio of two binding constants. Any references/comments most welcome. - Friedrich - ------------------------------------------------------------------------------- Dr. Friedrich Rippmann work: c/o E.MERCK home: Pha Fo Chem, Drug Design Schroederstrasse 72 6100 Darmstadt 6900 Heidelberg 1 POBox 4119 +49-6221-413366 +49-6151-726290 Email: bio320@cvx12.inet.dkfz-heidelberg.de Fax ... 710757 -------------------------------------------------------------------------------- >>>>End original posting<<<< Thanks a lot to all who replied. Here comes the summary: Rebecca Wade (wade@embl-heidelberg.de) writes: Just saw your question on the comp. chem. network! I have lots of refs giving energies of h-bonds from 0.0 to 6+ kcal/mol. An interesting, although maybe out of date ref is: Fersht,A. (87) TIBS 12 p301. There are many subsequent papers. The energetics depend on the chemical nature of the donors and acceptors, the h-bond geometry and whether solvent compensation can occur or not. The last factor means that most binding energy is probably achieved through hydrophobic groups binding and specificity is provided by h-bonds. But methods like GRID and LUDI stress h-bonding for binding energy and specificity. (incidently, you could use the GRID energy and h-bond functions if you want to estimate your h-bond energy difference). ( I have refs for this if you are interested). From: mes@atlas.chemistry.uakron.edu (mary ellen scott) Not so simple huh? I'm doing hydrogen bondong studies between sorbitol and sorbitol dehydrogenase. Lots of papers by Steven Withers- . My approach is kinetics then use homology model of SDG.pdb to look at active sight. modeling approach; Minimization energy of protein " protein + cofactor " protein + cofactor + substrate " protein + cofactor + analogues different substrate analogues substrate polyol all OH - haccept + hdonate polyol substitute F for OH at each position - haccept polyol substitute H for OH " - neither kinetics: deltadelta G# = RT ln( (Vm/Km)subst/(Vm/Km)unsub) These values represent the minimum hbond strengths at each position in the transition state. For ground state analysis or binding, need to design and synthesize inhibitors which are not substrates. REF: Fluorinated Carbohydrates: Chemical and Biochemical Aspects ACS Symposium Series,#374: ed N.F. Taylor, 1988 ISBN 0-8412-1492-1, Steve Withers has more papers in Biochemistry 1992 Percival, M.D. and Withers, S., Biochemistry, # 31 pp 498-505, 1992. Hope this helps in your research. I am writing my thesis now and would like to critique this approach. So if you have any suggestions let me know and would you share with me any responses you receive from your querry? Thanks. Sincerely Mary Ellen