Dear Amber users!
I'd like to rise small discussion ataking as the example Amber's mmpbsa.py
output calculated for my test cases. I've performed 2 simulations of 2
water-soluble proteins in complex with the same small ligand- cyclic-GMP
using default GB model ( gb=2) with the enthropy estimation using
quasi-harmonic analysis for the calculated MD trajectory of 100ns. As the
result I've obtained below results for complex 1 and complex 2:
Complex 1:
ENTROPY RESULTS (QUASI-HARMONIC APPROXIMATION)
Translational Rotational Vibrational Total
Complex: 16.6624 17.1013 3651.2484 3685.0121
Receptor: 16.6490 17.0914 3628.1003 3661.8407
Ligand: 12.9320 10.4221 23.5061 46.8602
DELTA S: -12.9185 -10.4123 -0.3581 -23.6889
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
Differences (Complex - Receptor - Ligand):
Energy Component Average Std. Dev. Std. Err. of
Mean
-------------------------------------------------------------------------------
VDWAALS -39.6926 4.4095
0.0481
EEL -67.9190 18.3714
0.2004
EGB 60.5076 16.5156
0.1801
ESURF -4.6620 0.2255
0.0025
DELTA G gas -107.6115 19.2880
0.2104
DELTA G solv 55.8456 16.4240
0.1791
DELTA TOTAL -51.7659 5.3246
0.0581
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
Using Quasi-harmonic Entropy Approximation: DELTA G binding = -28.0770
-------------------------------------------------------------------------------
Complex 2
ENTROPY RESULTS (QUASI-HARMONIC APPROXIMATION)
Translational Rotational Vibrational Total
Complex: 16.6988 17.2134 4195.0310 4228.9435
Receptor: 16.6860 17.2044 4170.7959 4204.6866
Ligand: 12.9320 10.3756 21.8699 45.1775
DELTA S: -12.9191 -10.3667 2.3652 -20.9206
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
Differences (Complex - Receptor - Ligand):
Energy Component Average Std. Dev. Std. Err. of
Mean
-------------------------------------------------------------------------------
VDWAALS -44.2846 3.8162
0.0399
EEL -171.1662 16.1727
0.1691
EGB 166.6577 13.0204
0.1361
ESURF -4.9646 0.2213
0.0023
DELTA G gas -215.4508 15.7887
0.1651
DELTA G solv 161.6931 12.9734
0.1356
DELTA TOTAL -53.7578 6.0216
0.0630
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
Using Quasi-harmonic Entropy Approximation: DELTA G binding = -32.8372
-------------------------------------------------------------------------------
These results suggests that (i) relative affinity (which corresponds to the
tightness of the complex and its time-life) should be higher in case of
complex 2 (lover dG) and (ii) the gain in dG in the second case is cased by
the lover entropy penalty (-20 vs -23 kccal/mol) having the same dH values
for both complexes. Are these suggestions correct?
(iii) On what output details should I paid begger attention if I'd like to
define which term (e.g electrostatic or hydrophobic ) has largest
contribution to the dH ? E.g from those outputs I've noticed the same dH
for both complexes but big deference in values of EEL and EGB for both
complexes. For instance taking complex 2 does the lover EEL indicate on
stronger electrostatic forces between protein and ligand and the higher EGB
point on the higher desolvation penalty (masking polar ligand from the
polar solvent) ?
I'll be thankful for any suggestions and further discussions as well as for
any provided examples for the analysis of the same outputs.
James
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Received on Sun May 11 2014 - 01:00:02 PDT
