Dear Colleagues, I see I should quote the last sentence of our abstract of Bradbrook et al 1998:-
....This work demonstrates the difficulty in relating structure to thermodynamics, but suggests that dynamic models are needed to provide a more complete picture of ligand - receptor interactions. Best wishes, John Prof John R Helliwell DSc On Wed, Oct 13, 2010 at 3:35 PM, Martyn Winn <martyn.w...@stfc.ac.uk> wrote: > This is all true. And I think the bottom line is that it is extremely > non-trivial to get a meaningful number. > > The Amber MM-PBSA script is the best established one. We have an > equivalent CHARMM-based script at: > http://www.cse.scitech.ac.uk/cbg/software/charmm/ > > But I guess this is beyond the original question. A simpler option (but > more approximate) would be to run the PDB of the modelled complex > through PISA (online or CCP4 version) and look at the results for the > protein ligand interface. > > Cheers > Martyn > > On Wed, 2010-10-13 at 15:15 +0100, Robert Esnouf wrote: >> Dear Rex, >> >> It certainly matters what you mean by the "energy" of a >> protein ligand complex. And whether you are comparing a series >> of related similar structures or looking for an "absolute" >> energy. >> >> The problem is that there is no such thing as an "absolute" >> energy, it is always relative to something else. Typically, >> you might calculate the the binding free energy (delta G) for >> the components in aqueous solution. If you were looking at the >> (small) differences between related structures then you'd look >> at the change (delta delta G) and hope the other errors >> largely cancel out. >> >> One method for which there is substantial literature is based >> on Amber simulations. There are even sample scripts to do the >> correct job. You simulate the complex in a water box and >> sample the conformation every so many steps. You then discard >> the waters and use something like the Poisson-Boltmann method >> to estimate solvation free energies for the complex and the >> isolated components. The difference is then your estimation of >> the binding free energy. >> >> In all such simulations it is the effect of the solvent >> (partial charges, dielectric properties and entropic effects) >> that are likely to dominate the calculation. You have to do >> your best to include them as realistically as possible. >> >> Amber is not free, but not expensive and your institution >> probably already has a site licence. Other simulation programs >> would also do the job (probably just as well!) but I am not >> aware they have available scripts. >> >> >> Best wishes, >> Robert >> >> -- >> >> Dr. Robert Esnouf, >> University Research Lecturer >> and Head of Research Computing, >> Wellcome Trust Centre for Human Genetics, >> Roosevelt Drive, Oxford OX3 7BN, UK >> >> Emails: rob...@strubi.ox.ac.uk Tel: (+44) - 1865 - 287783 >> and rob...@esnouf.com Fax: (+44) - 1865 - 287547 > > -- > *********************************************************************** > * * > * Dr. Martyn Winn * > * * > * STFC Daresbury Laboratory, Daresbury, Warrington, WA4 4AD, U.K. * > * Tel: +44 1925 603455 E-mail: martyn.w...@stfc.ac.uk * > * Fax: +44 1925 603634 Skype name: martyn.winn * > * URL: http://www.ccp4.ac.uk/martyn/ * > *********************************************************************** > -- Professor John R Helliwell DSc
