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

Xioling Chuang xioling_c at hotmail.com
Wed Nov 2 19:48:57 PDT 2011


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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