Re: [ccp4bb] protein ligand energy
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
Re: [ccp4bb] protein ligand energy
Rex Palmer wrote: Can anyone reccomend a free download program that will calculate the energy of a protein/ligand complex? The ligand has been modelled in. Thanks Rex Palmer Birkeck College Hi Rex, I think any refinement program such as CNS will do this - problem is, since these programs are aimed at refinement, you need a file containing observations (crystallographic data or NMR observations file). There is also within CNS the input file model_stats.inp, I have no idea of what this one does (I cannot remember if I have used it in the past), if it provides the energy terms that you may require. example (from a minimize run): | Etotal =0.14E+07 grad(E)=38.876 E(BOND)=5061.584 E(ANGL)=8964.251 | | E(DIHE)=8542.700 E(IMPR)=2466.346 E(VDW )=6787.298 E(PVDW)=27.910 | | E(XREF)=0.13E+07 Here there is an X-ray energy term, obviously (this is taken from a refinement run, at the beginning of energy minimization). Now of course perhaps this is not what you are looking for. Fred.
Re: [ccp4bb] protein ligand energy
Dear Rex, Not withstanding Fred's reply just to also mention that in our study:- G.M. Bradbrook, T. Gleichmann, S.J. Harrop, J. Habash, J. Raftery, A.J. Kalb (Gilboa), J. Yariv, I H Hillier and J.R. Helliwell “X–ray and molecular dynamics studies of concanavalin A glucoside and mannoside complexes: Relating structure to thermodynamics of binding” (1998) Faraday Transactions 94(11), 1603–1611. we found it important to undertake MD, from the starting crystal structures, to get reasonable cross-checks against the available calorimetry data. Greetings, John Professor John R Helliwell DSc On Wed, Oct 13, 2010 at 12:43 PM, Rex Palmer rex.pal...@btinternet.com wrote: Can anyone reccomend a free download program that will calculate the energy of a protein/ligand complex? The ligand has been modelled in. Thanks Rex Palmer Birkeck College
Re: [ccp4bb] protein ligand energy
Would APBS do what you want? http://www.poissonboltzmann.org/apbs/ It has interfaces with Pymol, VMD and others... From: Rex Palmer rex.pal...@btinternet.com To: CCP4BB@JISCMAIL.AC.UK Sent: Wed, October 13, 2010 6:43:49 AM Subject: [ccp4bb] protein ligand energy Can anyone reccomend a free download program that will calculate the energy of a protein/ligand complex? The ligand has been modelled in. Thanks Rex Palmer Birkeck College
Re: [ccp4bb] protein ligand energy
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.comFax: (+44) - 1865 - 287547
Re: [ccp4bb] protein ligand energy
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.comFax: (+44) - 1865 - 287547 -- *** * * * Dr. Martyn Winn * * * * STFC Daresbury Laboratory, Daresbury, Warrington, WA4 4AD, U.K. * * Tel: +44 1925 603455E-mail: martyn.w...@stfc.ac.uk* * Fax: +44 1925 603634Skype name: martyn.winn * * URL: http://www.ccp4.ac.uk/martyn/ * ***
