ADL: "binding energy" vs. "estimated free energy of binding"

Mark Swingle mswingle at jaguar1.usouthal.edu
Fri Nov 4 15:09:06 PDT 2011


In the first case, total internal energy and unbound system energy are equal 
and cancel each other out in the expression for free energy, so 
FE=intermolecular energy + torsional free energy. In the second case, there is 
a contribution to the total internal energy from receptor-receptor 
interactions (-2.38kcal/mol in this case) that should contribute to the FE. It 
looks like the clustering algorithm is ignoring this and assuming that total 
internal energy = ligand internal energy. 


On Friday, November 04, 2011 12:26:26 am Corzell Brown wrote:
> I believe that it is standard to report the lowest binding energy
> conformation.
> 
> > From: xioling_c at hotmail.com
> > To: autodock at scripps.edu
> > Date: Thu, 3 Nov 2011 03:48:57 +0100
> > Subject: ADL: "binding energy" vs. "estimated free energy of binding"
> > 
> > 
> > Dear All,
> > 
> > I used AutoDock4.2 to re-dock a ligand-protein system using 2 approaches
> > .
> > 
> > 1) By fixing protein as rigid, I got the lowest binding energy (in the
> > table of CLUSTERING HISTOGRAM, run #43) = -9.69 kcal/mol, which is equal
> > to  the Estimated Free Energy of Binding for the corresponding #Run.
> > 
> > 2) By allowing the flexibility of one amino acid in active site of the
> > protein, the obtained "binding energy" and "Estimated Free Energy of
> > Binding" are different (-9.34 and -11.72 kcal/mol, respectively). Why
> > these energies are different?
> > Are they different meaning?
> > Which one should I report?
> > 
> > Thank you very much in advance for your suggestions.
> > 
> > Best,
> > Xioling
> > 
> > ===============================
> > 
> > Output for the 1st approach
> > 
> > ===============================
> > -------------------------------------------------------------------------
> > ---------------------------------
> > 
> > Clus | Lowest    | Run | Mean      | Num | Histogram
> > -ter | Binding   |     | Binding   | in  |
> > Rank | Energy    |     | Energy    | Clus|    5    10   15   20   25   30
> >   35
> > _____|___________|_____|___________|_____|____:____|____:____|____:____|
> > ____:___
> > 
> >    1 |     -9.69 |  43 |     -9.69 |  50
> >    |##################################################
> > 
> > _____|___________|_____|___________|_____|_______________________________
> > _______
> > 
> > Number of multi-member conformational clusters found = 1, out of 50 runs.
> > 
> >         RMSD TABLE
> >         __________
> > 
> > _____________________________________________________________________
> > 
> > Rank | Sub- | Run  | Binding   | Cluster | Reference       | Grep
> > 
> >      | Rank |      | Energy    | RMSD    | RMSD            | Pattern
> > 
> > _____|______|______|___________|_________|_________________|___________
> > 
> >    1      1     43       -9.69      0.00      0.96           RANKING
> >    1      2     44       -9.69      0.01      0.96           RANKING
> >    1      3     38       -9.69      0.01      0.96           RANKING
> >    1      4     42       -9.69      0.01      0.97           RANKING
> > 
> > .
> > .
> > .
> > MODEL       43
> > USER    Run = 43
> > USER    Cluster Rank = 1
> > USER    Number of conformations in this cluster = 50
> > USER
> > USER    RMSD from reference structure       = 0.965 A
> > USER
> > USER    Estimated Free Energy of Binding    =   -9.69 kcal/mol 
> > [=(1)+(2)+(3)-(4)] USER    Estimated Inhibition Constant, Ki   =   78.26
> > nM (nanomolar)  [Temperature = 298.15 K] USER
> > USER    (1) Final Intermolecular Energy     =  -11.48 kcal/mol
> > USER        vdW + Hbond + desolv Energy     =  -10.64 kcal/mol
> > USER        Electrostatic Energy            =   -0.84 kcal/mol
> > USER    (2) Final Total Internal Energy     =   -0.19 kcal/mol
> > USER    (3) Torsional Free Energy           =   +1.79 kcal/mol
> > USER    (4) Unbound System's Energy         =   -0.19 kcal/mol
> > 
> > 
> > ===============================
> > Output for the 2nd approach
> > ===============================
> > 
> >         CLUSTERING HISTOGRAM
> >         ____________________
> > 
> > _________________________________________________________________________
> > _______
> > 
> > Clus | Lowest    | Run | Mean      | Num | Histogram
> > -ter | Binding   |     | Binding   | in  |
> > Rank | Energy    |     | Energy    | Clus|    5    10   15   20   25   30
> >   35
> > _____|___________|_____|___________|_____|____:____|____:____|____:____|
> > ____:___
> > 
> >    1 |     -9.34 |  45 |     -9.32 |  50
> >    |##################################################
> > 
> > _____|___________|_____|___________|_____|_______________________________
> > _______
> > 
> > Number of multi-member conformational clusters found = 1, out of 50 runs.
> > 
> >         RMSD TABLE
> >         __________
> > 
> > __________________________________________________________________
> > 
> > Rank | Sub- | Run  | Binding   | Cluster | Reference       | Grep
> > 
> >      | Rank |      | Energy    | RMSD    | RMSD            | Pattern
> > 
> > _____|______|______|___________|_________|_________________|___________
> > 
> >    1      1     45       -9.34      0.00      0.90           RANKING
> >    1      2     24       -9.33      0.03      0.91           RANKING
> > 
> > .
> > .
> > .
> > 
> > MODEL       45
> > USER    Run = 45
> > USER    Cluster Rank = 1
> > USER    Number of conformations in this cluster = 50
> > USER
> > USER    RMSD from reference structure       = 0.896 A
> > USER
> > USER    Estimated Free Energy of Binding    =  -11.72 kcal/mol 
> > [=(1)+(2)+(3)-(4)] USER    Estimated Inhibition Constant, Ki   =    2.57
> > nM (nanomolar)  [Temperature = 298.15 K] USER
> > USER    (1) Final Intermolecular Energy     =  -11.13 kcal/mol
> > USER        vdW + Hbond + desolv Energy     =   -9.25 kcal/mol
> > USER        Electrostatic Energy            =   -0.84 kcal/mol
> > USER        Moving Ligand-Fixed Receptor    =  -10.09 kcal/mol
> > USER        Moving Ligand-Moving Receptor   =   -1.04 kcal/mol
> > USER    (2) Final Total Internal Energy     =   -2.57 kcal/mol
> > USER        Internal Energy Ligand          =   -0.19 kcal/mol
> > USER        Internal Moving-Fixed Receptor  =   -2.38 kcal/mol
> > USER        Internal Moving-Moving Receptor =   +0.00 kcal/mol
> > USER    (3) Torsional Free Energy           =   +1.79 kcal/mol
> > USER    (4) Unbound System's Energy         =   -0.19 kcal/mol
> > 
> > 
> > 
> > ________________________________________________
> > --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
> 
> ________________________________________________
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