To put some numbers to what David said, here's an experimental paper on a well-studied drug-protein complex: http://pubs.acs.org/doi/pdf/10.1021/bi001013s
the entropic contribution of HIV-1 protease inhibitor binding is about 3x bigger than the enthalpic contribution for all 4 drugs studied there. I'm not sure if that's a special case, but if you're leaving out entropy you are at the very least doing an uncontrolled approximation - you don't know how big the term is you're missing, and it could be the dominant term. Sander On 21 Oct 2010, at 10:45 , David van der Spoel wrote: > On 2010-10-21 10.39, Ehud Schreiber wrote: >> Actually, I believe that using the energy difference, Delta E, as an >> approximation to the free energy difference, Delta G, is a valid >> approach (which I'm considering myself). The entropic contribution to >> Delta G, namely -T Delta S, may be less prominent than Delta E. >> In addition, Delta S can be approximated by various means - see e.g. >> Doig& Sternberg 1995. I understand that such an approach is utilized in >> the Accelrys Discovery Studio. >> Obviously, this is an approximation that might be too crude for some >> applications. > > As a simple example the hydrophobic effect at room temperature is largely due > to the entropy of the water [ at high temp it is due to the enthalpy of the > water ]. > > Since the hydrophobic effect is involved in all ligand binding it seems quite > hopeless to get any reliable numbers when neglecting entropy. No referee will > buy that - I wouldn't. > >> >> What do you think? >> >> ------------------------------------------------------------------------ >> -- >> >> On Oct 21, 2010, at 09:25 , Sander Pronk wrote: >> >> Hi Mohsen, >> >> The mean energy difference is only one component of the free energy >> difference. >> >> Before you go any further I'd suggest reading a good book on molecular >> simulations, like 'Understanding Molecular Simulations' by Frenkel and >> Smit. >> >> There's a good reason free energy calculations cover over half of that >> book. >> >> Sander >> >> >> On Oct 21, 2010, at 09:18 , mohsen ramezanpour wrote: >> >>> Dear Justin >>> >>> If I do two MD simulations for a short time in the same >> conditions(of course separately for protein and drug) >>> and calculate total energy of each one and sum them with each other >> as E1 as nonbonding free energy of system. >>> then a MD simulation for Protein-drug system in the same condition and >> calculate it's total energy too as E2 as bound system . >>> what does (E1-E2)mean? >>> I think it is binding free energy,Is not it? >>> in the other hand when we are working on NPT ensamble it means Gibbs >> free energy is the main energy and our total energy is equal to Gibbs >> free energy. >>> Then,what is the problem? > > > -- > David van der Spoel, Ph.D., Professor of Biology > Dept. of Cell & Molec. Biol., Uppsala University. > Box 596, 75124 Uppsala, Sweden. Phone: +46184714205. > sp...@xray.bmc.uu.se http://folding.bmc.uu.se > -- > gmx-users mailing list gmx-users@gromacs.org > http://lists.gromacs.org/mailman/listinfo/gmx-users > Please search the archive at > http://www.gromacs.org/Support/Mailing_Lists/Search before posting! > Please don't post (un)subscribe requests to the list. Use the www interface > or send it to gmx-users-requ...@gromacs.org. > Can't post? Read http://www.gromacs.org/Support/Mailing_Lists -- gmx-users mailing list gmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
