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

Corzell Brown corzellbrown at hotmail.com
Thu Nov 3 22:26:26 PDT 2011


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
> 
> 
>  		 	   		  
> ________________________________________________
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