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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: [log in to unmask] Tel: (+44) - 1865 - 287783 > and [log in to unmask] Fax: (+44) - 1865 - 287547 -- *********************************************************************** * * * Dr. Martyn Winn * * * * STFC Daresbury Laboratory, Daresbury, Warrington, WA4 4AD, U.K. * * Tel: +44 1925 603455 E-mail: [log in to unmask] * * Fax: +44 1925 603634 Skype name: martyn.winn * * URL: http://www.ccp4.ac.uk/martyn/ * ***********************************************************************