Hi,
I came across a problem in MMPBSA calculation recently. The binding free energy is extremely high especially for the VDWAALS and 1-4 VDW part.
I examine the "_MMPBSA_complex.pdb" file in VMD and find that the structure of the ligand crushes while the amino acids are OK.
I guess there are some inconsistencies between the prmtop file and the trajectories of the ligand. But I couldn't figure out the point. Could you give me some suggestions?
Here is the "FINAL_RESULTS_MMPBSA.dat" file:
|Input file:
|--------------------------------------------------------------
|Input file for running PB and GB
|&general
| startframe=201, verbose=1,
|# entropy=1,
|/
|&gb
| igb=2, saltcon=0.100
|/
|&pb
| istrng=0.100,
|/
|
|
|--------------------------------------------------------------
|Solvated complex topology file: 3BWY_neg_lut5_LYN_SAM.prmtop
|Complex topology file: 3BWY_neg_lut5_LYN_SAM_nosolv.prmtop
|Receptor topology file: 3BWY_neg_lut5_LYN_SAM_noH_nolut.prmtop
|Ligand topology file: neg_luteolin5.prmtop
|Initial mdcrd(s): production3.mdcrd
|
|Best guess for receptor mask: ":1-216"
|Best guess for ligand mask: ":217"
|Ligand residue name is "LUT"
|
|Calculations performed using 200 frames.
|Poisson Boltzmann calculations performed using internal PBSA solver in sander.
|
|All units are reported in kcal/mole.
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
GENERALIZED BORN:
WARNING: INCONSISTENCIES EXIST WITHIN 1-4 NON-BONDED TERMS.
CHECK YOUR INPUT FILES AND SYSTEM SETUP. THESE RESULTS MAY NOT BE RELIABLE (check differences)!
The most common cause of this is inconsistent charge definitions across topology files.
Complex:
Energy Component Average Std. Dev. Std. Err. of Mean
-------------------------------------------------------------------------------
VDWAALS 21006150336550031360.0000 212017833520375070720.0000 15029545730918023168.0000
EEL -7468.4040 1236.3948 87.6457
1-4 VDW 4282229701684408877056.0000 42099142055861577318400.0000 2984329055037626515456.0000
1-4 EEL 982.2488 968.2529 68.6376
EGB -5610.6208 465.7548 33.0165
ESURF 55.2802 2.3492 0.1665
G gas 4303235852020958101504.0000 42097542547851609899008.0000 2984215668921074188288.0000
G solv -5555.3406 465.9751 33.0321
TOTAL 4303235852020958101504.0000 42097542547851609899008.0000 2984215668921074188288.0000
Receptor:
Energy Component Average Std. Dev. Std. Err. of Mean
-------------------------------------------------------------------------------
VDWAALS 21005544796506038272.0000 212017893069718487040.0000 15029549952259053568.0000
EEL -7695.4620 1235.8941 87.6102
1-4 VDW 4281985119177865691136.0000 42099166792161559576576.0000 2984330808547440328704.0000
1-4 EEL 1443.2652 958.3304 67.9342
EGB -5608.2873 478.6512 33.9307
ESURF 55.9342 2.4598 0.1744
G gas 4302990663974364119040.0000 42097567469026228043776.0000 2984217435536303325184.0000
G solv -5552.3531 478.9203 33.9498
TOTAL 4302990663974364119040.0000 42097567469026228043776.0000 2984217435536303325184.0000
Ligand:
Energy Component Average Std. Dev. Std. Err. of Mean
-------------------------------------------------------------------------------
VDWAALS 141210847715258.3125 1666571428388523.0000 118140116238851.9688
EEL 252.6849 97.0809 6.8819
1-4 VDW 244582506544392416.0000 3440575681575656960.0000 243895943507772832.0000
1-4 EEL -461.0165 83.8380 5.9431
EGB -164.6754 30.2935 2.1475
ESURF 2.6234 0.2556 0.0181
G gas 244723717392107936.0000 3440566046845218816.0000 243895260519840544.0000
G solv -162.0521 30.3183 2.1492
TOTAL 244723717392107904.0000 3440566046845219328.0000 243895260519840576.0000
Differences (Complex - Receptor - Ligand):
Energy Component Average Std. Dev. Std. Err. of Mean
-------------------------------------------------------------------------------
VDWAALS 464329196269944.4375 6456047927338494.0000 457657103432328.0625
EEL -25.6269 102.8246 7.2890
1-4 VDW -488.0288 4686.7461 332.2346
1-4 EEL -0.0000 0.0001 0.0000
EGB 162.3420 79.1399 5.6101
ESURF -3.2774 0.9013 0.0639
DELTA G gas 464329196191104.1875 6456047927344164.0000 457657103432730.0000
DELTA G solv 159.0645 79.0900 5.6065
DELTA G binding = 464329196191261.6875 +/- 6456047927344175.0000 457657103432730.8125
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
POISSON BOLTZMANN:
WARNING: INCONSISTENCIES EXIST WITHIN 1-4 NON-BONDED TERMS.
CHECK YOUR INPUT FILES AND SYSTEM SETUP. THESE RESULTS MAY NOT BE RELIABLE (check differences)!
The most common cause of this is inconsistent charge definitions across topology files.
Complex:
Energy Component Average Std. Dev. Std. Err. of Mean
-------------------------------------------------------------------------------
VDWAALS 21006150336550055936.0000 212017833520375234560.0000 15029545730918033408.0000
EEL -7468.4040 1236.3948 87.6457
1-4 VDW 4282229701684408877056.0000 42099142055861577318400.0000 2984329055037626515456.0000
1-4 EEL 982.2488 968.2529 68.6376
EPB -4320.4560 369.9319 26.2238
ECAVITY 53.0443 0.8530 0.0605
G gas 4303235852020958101504.0000 42097542547851609899008.0000 2984215668921074188288.0000
G solv -4267.4117 369.6239 26.2019
TOTAL 4303235852020958101504.0000 42097542547851609899008.0000 2984215668921074188288.0000
Receptor:
Energy Component Average Std. Dev. Std. Err. of Mean
-------------------------------------------------------------------------------
VDWAALS 21005544796506054656.0000 212017893069718683648.0000 15029549952259067904.0000
EEL -7695.4620 1235.8941 87.6102
1-4 VDW 4281985119177865691136.0000 42099166792161559576576.0000 2984330808547440328704.0000
1-4 EEL 1443.2652 958.3304 67.9342
EPB -4348.3379 384.4561 27.2534
ECAVITY 53.2268 0.8828 0.0626
G gas 4302990663974364119040.0000 42097567469026228043776.0000 2984217435536303325184.0000
G solv -4295.1110 384.1966 27.2350
TOTAL 4302990663974364119040.0000 42097567469026228043776.0000 2984217435536303325184.0000
Ligand:
Energy Component Average Std. Dev. Std. Err. of Mean
-------------------------------------------------------------------------------
VDWAALS 141210847715258.4062 1666571428388523.7500 118140116238852.0312
EEL 252.6849 97.0809 6.8819
1-4 VDW 244582506544392416.0000 3440575681575656960.0000 243895943507772832.0000
1-4 EEL -461.0165 83.8380 5.9431
EPB -143.9965 26.3195 1.8657
ECAVITY 1.8704 0.3239 0.0230
G gas 244723717392107936.0000 3440566046845218816.0000 243895260519840544.0000
G solv -142.1260 26.3208 1.8658
TOTAL 244723717392107904.0000 3440566046845219328.0000 243895260519840576.0000
Differences (Complex - Receptor - Ligand):
Energy Component Average Std. Dev. Std. Err. of Mean
-------------------------------------------------------------------------------
VDWAALS 464329196269953.1875 6456047927338652.0000 457657103432339.3125
EEL -25.6269 102.8246 7.2890
1-4 VDW -488.0288 4686.7461 332.2346
1-4 EEL -0.0000 0.0001 0.0000
EPB 171.8783 85.5514 6.0646
ECAVITY -2.0530 0.3528 0.0250
DELTA G gas 464329196191114.7500 6456047927344320.0000 457657103432741.0625
DELTA G solv 169.8253 85.5208 6.0624
DELTA G binding = 464329196191280.3750 +/- 6456047927344334.0000 457657103432742.0625
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
Cao Yang,
Zhejiang University, China
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Received on Tue May 08 2012 - 03:00:04 PDT
