AMBER Archive (2009)

Subject: [AMBER] Docking with Amber

From: Jordan, Brad (jbjordan_at_amgen.com)
Date: Mon Aug 31 2009 - 15:01:15 CDT

Hi all - I'm attempting to dock a small molecule to a protein binding pocket using intermolecular NOE restraints. I'm having some problems and was hoping someone could help out. Here is what I've done so far:

 1. created a .mol2 file of the ligand and used antechamber to get it to the correct format. I have generated the files ligand.frcmod and ligand.prepi
 2. protonated the PDB file of the protein and created a merged.pdb file containing the protein and ligand coordinates.
 3. Used Tleap to convert these files to prmtop and coordinate files. Here's my Leap script:

Source leaprc.ff99
Source leaprc.gaff
Ligand = loadAmberparams ligand.frcmod
LoadAmberPrep ligand.prepi
Model = loadPDB merged.pdb
Saveamberparm model prmtop complex.x

I then use the prmtop and coordinate file as input to minimization and MD runs. First, I just try a simple minimization without restraints and get the following erroneous output.

&cntrl
     imin=1,maxcyc=200,ncyc=50,ntpr=20,ntb=0,ntr=1,igb=1
&end
Group restraints
 1.0
RES 10-110
END
END

--------------------------------------------------------------------------------
   1. RESOURCE USE:
--------------------------------------------------------------------------------

| Flags:
| New format PARM file being parsed.
| Version = 1.000 Date = 08/28/09 Time = 10:07:29
 NATOM = 2042 NTYPES = 15 NBONH = 1023 MBONA = 1038
 NTHETH = 2325 MTHETA = 1407 NPHIH = 4353 MPHIA = 2609
 NHPARM = 0 NPARM = 0 NNB = 11285 NRES = 126
 NBONA = 1038 NTHETA = 1407 NPHIA = 2609 NUMBND = 47
 NUMANG = 95 NPTRA = 37 NATYP = 36 NPHB = 0
 IFBOX = 0 NMXRS = 52 IFCAP = 0 NEXTRA = 0

| Memory Use Allocated Used
| Real 20000000 83920
| Hollerith 400000 12380
| Integer 60000000 107369
| Duplicated 0 dihedrals
| Duplicated 0 dihedrals

--------------------------------------------------------------------------------
   2. CONTROL DATA FOR THE RUN
--------------------------------------------------------------------------------

General flags:
     imin = 1, nmropt = 0

Nature and format of input:
     ntx = 1, irest = 0, ntrx = 1

Nature and format of output:
     ntxo = 1, ntpr = 20, ntrx = 1, ntwr = 500
     iwrap = 0, ntwx = 0, ntwv = 0, ntwe = 0
     ioutfm = 0, ntwprt = 0, idecomp = 0, rbornstat= 0

Potential function:
     ntf = 1, ntb = 0, igb = 1, nsnb = 25
     ipol = 0, gbsa = 0
     dielc = 1.00000, cut = 8.00000, intdiel = 1.00000
     saltcon = 0.00000, offset = 0.09000, gbalpha= 1.00000
     gbbeta = 0.00000, gbgamma = 0.00000, surften = 0.00500
     scnb = 2.00000, scee = 1.20000

Frozen or restrained atoms:
     ibelly = 0, ntr = 1

Energy minimization:
     maxcyc = 200, ncyc = 50, ntmin = 1
     dx0 = 0.01000, dxm = 0.50000, drms = 0.00010

    LOADING THE CONSTRAINED ATOMS AS GROUPS

   5. REFERENCE ATOM COORDINATES

    ----- READING GROUP 1; TITLE:
 Group restraints

     GROUP 1 HAS HARMONIC CONSTRAINTS 1.00000
      GROUP 1 CONSISTS OF RESIDUE97110

      Number of atoms in this group = 0
    ----- END OF GROUP READ -----

--------------------------------------------------------------------------------
   3. ATOMIC COORDINATES AND VELOCITIES
--------------------------------------------------------------------------------

 begin time read from input coords = 0.000 ps

 Number of triangulated 3-point waters found: 0

--------------------------------------------------------------------------------
   4. RESULTS
--------------------------------------------------------------------------------

   NSTEP ENERGY RMS GMAX NAME NUMBER
      1 NAN NAN 0.0000E+00 N 1

 BOND = 101.3867 ANGLE = 231.9497 DIHED = 1194.9679
 VDWAALS = ************* EEL = -7343.2759 EGB = nan
 1-4 VDW = 729.7817 1-4 EEL = 5409.3719 RESTRAINT = 0.0000

   NSTEP ENERGY RMS GMAX NAME NUMBER
     20 NAN NAN 0.0000E+00 N 1

 BOND = nan ANGLE = nan DIHED = 553.6600
 VDWAALS = nan EEL = nan EGB = nan
 1-4 VDW = nan 1-4 EEL = nan RESTRAINT = 0.0000

   NSTEP ENERGY RMS GMAX NAME NUMBER
     40 NAN NAN 0.0000E+00 N 1

 BOND = nan ANGLE = nan DIHED = 553.6600
 VDWAALS = nan EEL = nan EGB = nan
 1-4 VDW = nan 1-4 EEL = nan RESTRAINT = 0.0000

     .... RESTARTED DUE TO LINMIN FAILURE ...

     .... RESTARTED DUE TO LINMIN FAILURE ...

   NSTEP ENERGY RMS GMAX NAME NUMBER
     60 NAN NAN 0.0000E+00 N 1

 BOND = nan ANGLE = nan DIHED = 553.6600
 VDWAALS = nan EEL = nan EGB = nan
 1-4 VDW = nan 1-4 EEL = nan RESTRAINT = 0.0000

     .... RESTARTED DUE TO LINMIN FAILURE ...

     .... RESTARTED DUE TO LINMIN FAILURE ...

     .... RESTARTED DUE TO LINMIN FAILURE ...

                    FINAL RESULTS

   NSTEP ENERGY RMS GMAX NAME NUMBER
     71 NAN NAN 0.0000E+00 N 1

 BOND = nan ANGLE = nan DIHED = 553.6600
 VDWAALS = nan EEL = nan EGB = nan
 1-4 VDW = nan 1-4 EEL = nan RESTRAINT = 0.0000

     ***** REPEATED LINMIN FAILURE *****

--------------------------------------------------------------------------------
   5. TIMINGS
--------------------------------------------------------------------------------

| Highest rstack allocated: 22462
| Highest istack allocated: 4084

| Setup wallclock 0 seconds
| Nonsetup wallclock 43 seconds

I would appreciate any ideas as to what I'm doing wrong.

Thanks in advance.

Brad

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