Using Leap for the Complex

Directory for Complex Setup

% mkdir complex_setup
% cp ligand_setup/TAZ.frcmod ligand_setup/TAZ.mol2 complex_setup
% cp ligand_setup/taz_min.pdb complex_setup
% cp prot_setup/vm1_prot_min.pdb complex_setup/
% cd complex_setup
%

Use tleap to create input files for sander

First concatenate the protein and taz into the same pdb.

% cat vm1_prot_min.pdb taz_min.pdb >vm1_prot_taz.pdb
%

Edit the resulting file to remove the END and REMARK between the molecules in the pdb file (near the end of the file).

ATOM   4071  O   ARG   265      54.492  42.434  17.268
ATOM   4072  OXT ARG   265      55.734  43.387  18.800
TER   
END   
REMARK                                                              
ATOM      1  S1  TAZ     1      31.153  65.859  -7.439
ATOM      2  C2  TAZ     1      29.529  65.121  -7.510

should be

ATOM   4071  O   ARG   265      54.492  42.434  17.268
ATOM   4072  OXT ARG   265      55.734  43.387  18.800
TER   
ATOM      1  S1  TAZ     1      31.153  65.859  -7.439
ATOM      2  C2  TAZ     1      29.529  65.121  -7.510

Run tleap to make input files for min/md of the complex, create this input file for leap (xleap or tleap):
complex_setup.leapcmd

source leaprc.ff03 source leaprc.gaff mods=loadamberparams TAZ.frcmod TAZ=loadmol2 TAZ.mol2 complex=loadpdb vm1_prot_taz.pdb saveamberparm complex vm1_complex.prmtop vm1_complex.inpcrd go

Run tleap:

% tleap -f complex_setup.leapcmd

Create a pdb file for viewing:

% ambpdb -p vm1_complex.prmtop < vm1_complex.inpcrd > vm1_complex_initial.pdb

Run a minimization to clear up bad contacts

Create this file for sander input for simple minimization (same as for protein): min.in

Initial minimisation &cntrl imin=1, maxcyc=500, ncyc=200, cut=16, ntb=0, igb=1, /

Run Sander:

% sander -O -o complexmin.out -i min.in -c vm1_complex.inpcrd -p vm1_complex.prmtop -r vm1_complex_min.inpcrd
% ambpdb -p vm1_complex.prmtop < vm1_complex_min.inpcrd > vm1_complex_min.pdb

E We will use these input coordinates and prmtop to run a targeted md to dock the ligand into the active site where the fragment is located in the xray structure.

Go on to Targeted MD docking

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