AMBER Archive (2006)

Subject: AMBER: How to evaluate the binding energy of a ligand?

From: Alfredo Quevedo (alfredoq_at_mail.fcq.unc.edu.ar)
Date: Tue Apr 11 2006 - 12:53:50 CDT

Hello amber community.
I have a question that may be quite basic, but I have been trying to find a
definitive answer to the subject and I havent been able. I am trying to obtain
the free energy of binding of an organic molecule (treated with
antechamber) to
a protein. I started with the xray structure of the protein and obtained the
complex using Autodock 3. The summary of the dinamic simulation for both of
them are as follows:

Protein:

      A V E R A G E S O V E R 166675 S T E P S

NSTEP = 166675 TIME(PS) = 360.018 TEMP(K) = 300.00 PRESS = 0.0
Etot = -8899.0009 EKtot = 7105.4053 EPtot = -16004.4062
BOND = 1863.9468 ANGLE = 4945.9298 DIHED = 5505.1806
1-4 NB = 2113.7238 1-4 EEL = 28330.6576 VDWAALS = -4739.5288
EELEC = -45134.2717 EGB = -9051.7586 RESTRAINT = 0.0000
ESURF= 161.7143
------------------------------------------------------------------------------

      R M S F L U C T U A T I O N S

NSTEP = 166675 TIME(PS) = 360.018 TEMP(K) = 2.72 PRESS = 0.0
Etot = 104.0722 EKtot = 64.3817 EPtot = 83.7353
BOND = 36.1706 ANGLE = 53.5244 DIHED = 35.8815
1-4 NB = 19.6933 1-4 EEL = 60.2712 VDWAALS = 37.8560
EELEC = 667.8637 EGB = 652.1534 RESTRAINT = 0.0000
ESURF= 3.8105

Complex:

      A V E R A G E S O V E R 166675 S T E P S

NSTEP = 166675 TIME(PS) = 360.018 TEMP(K) = 299.91 PRESS = 0.0
Etot = -8943.0888 EKtot = 7127.9624 EPtot = -16071.0511
BOND = 1866.5459 ANGLE = 4959.0103 DIHED = 5540.5746
1-4 NB = 2129.1832 1-4 EEL = 28262.9367 VDWAALS = -4777.9134
EELEC = -45738.8612 EGB = -8472.0397 RESTRAINT = 0.0000
ESURF= 159.5123
------------------------------------------------------------------------------

      R M S F L U C T U A T I O N S

NSTEP = 166675 TIME(PS) = 360.018 TEMP(K) = 2.83 PRESS = 0.0
Etot = 104.3777 EKtot = 67.3769 EPtot = 75.1659
BOND = 37.0625 ANGLE = 54.0541 DIHED = 39.2921
1-4 NB = 19.6786 1-4 EEL = 51.4087 VDWAALS = 37.5984
EELEC = 617.1051 EGB = 612.5368 RESTRAINT = 0.0000
ESURF= 2.6848
------------------------------------------------------------------------------

When trying to calculate the binding energy as explained in Tutorial 2 I found
that (after running the dinamic over the ligand (not shown)) the
binding energy
is positive, indicating that the complex is not stabilized. This is not true
since Autodock finds a negative energy component for the affinity and also the
binding occurs experimentally. Which may be my problem??,
Thanks
Best wishes

Alfredo Quevedo
Dpto. Farmacia - Fac. Ciencias Quimicas
Universidad Nacional de Córdoba
Argentina

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