Tleap Inputs

The following examples demonstrate Tleap input configurations for preparing metal complexes and metalloprotein systems using AMBER 22. These templates provide a general framework and should be tailored to your specific system.

Metal Complex Input Example

This example corresponds to complex 7 from the original article describing the code:

source leaprc.gaff
source leaprc.water.tip3p
source leaprc.protein.ff19SB
loadamberparams frcmod.ionsjc_tip3p

# Define hybridization
addAtomTypes {
 { "Ru" "Ru" "sp3" }
 { "C1" "C" "sp3" }
 { "C2" "C" "sp3" }
 { "C3" "C" "sp3" }
 { "C4" "C" "sp3" }
 { "C5" "C" "sp3" }
 { "C6" "C" "sp3" }
 { "N1" "N" "sp3" }
 { "N2" "N" "sp3" }
}

# Load force field for metal complex
loadamberparams COMPLEX.frcmod
loadoff COMPLEX.lib

# Load protein + metal complex
mol = loadpdb "HB1.pdb"

# Save vacuum files
savepdb mol HB1_vacuum.pdb
saveamberparm mol HB1_vacuum.prmtop HB1_vacuum.inpcrd

# Solvate the system
solvateoct mol TIP3PBOX 10.0
check mol charge
addions mol Na+ 0.
addions mol Cl- 0

# Save solvated files
savepdb mol HB1_solvated.pdb
saveamberparm mol HB1_solvated.prmtop HB1_solvated.inpcrd
quit

Metalloprotein Input Example

These examples illustrate the setup for a metalloprotein system:

1- Using COMPLEX.lib

source leaprc.gaff
source leaprc.water.tip3p
loadamberparams frcmod.ionsjc_tip3p

# Load force field for residues and metal
loadamberparams COMPLEX.frcmod
# Load protein force field
source leaprc.protein.ff19SB
# Load library for residues and metals 
loadoff COMPLEX.lib
PRO1 = loadpdb "easyPARM_MetalloProtein.pdb"

# Define metal coordination bonds
bond PRO1.32.Zn1 PRO1.5.SG
bond PRO1.32.Zn1 PRO1.10.SG
bond PRO1.32.Zn1 PRO1.23.NE2
bond PRO1.32.Zn1 PRO1.27.NE2

# Link adjacent residues
bond PRO1.5.N PRO1.4.C
bond PRO1.5.C PRO1.6.N
bond PRO1.10.N PRO1.9.C
bond PRO1.10.C PRO1.11.N
bond PRO1.23.N PRO1.22.C
bond PRO1.23.C PRO1.24.N
bond PRO1.27.N PRO1.26.C
bond PRO1.27.C PRO1.28.N

# Save vacuum files
savepdb PRO1 1SP2_vacuum.pdb
saveamberparm PRO1 1SP2_vacuum.prmtop 1SP2_vacuum.inpcrd

# Solvate the system
solvateoct PRO1 TIP3PBOX 10.0
check PRO1 charge
addions PRO1 Cl- 0.
addions PRO1 Na+ 0.

# Save solvated files
saveamberparm PRO1 1SP2_solvated.prmtop 1SP2_solvated.inpcrd
savepdb PRO1 1SP2_solvated.pdb
quit

2- Using mol2 and hybridization files

source leaprc.gaff
source leaprc.water.tip3p
loadamberparams frcmod.ionsjc_tip3p

# Define hybridization
addAtomTypes {
 { "Zn" "Zn" "sp3" }
 { "s1" "S" "sp3" }
 { "s2" "S" "sp3" }
 { "n3" "N" "sp3" }
 { "n4" "N" "sp3" }
}

# Load force field for residues and metal
loadamberparams COMPLEX.frcmod

# Load protein force field
source leaprc.protein.ff19SB

# Load residues and metal
CY1 = loadmol2 "CY1.mol2"
CY2 = loadmol2 "CY2.mol2"
HI1 = loadmol2 "HI1.mol2"
HI2 = loadmol2 "HI2.mol2"
mol = loadmol2 "METAL.mol2"
PRO1 = loadpdb "easyPARM_MetalloProtein.pdb"

# Define metal coordination bonds
bond PRO1.32.Zn1 PRO1.5.SG
bond PRO1.32.Zn1 PRO1.10.SG
bond PRO1.32.Zn1 PRO1.23.NE2
bond PRO1.32.Zn1 PRO1.27.NE2

# Link adjacent residues
bond PRO1.5.N PRO1.4.C
bond PRO1.5.C PRO1.6.N
bond PRO1.10.N PRO1.9.C
bond PRO1.10.C PRO1.11.N
bond PRO1.23.N PRO1.22.C
bond PRO1.23.C PRO1.24.N
bond PRO1.27.N PRO1.26.C
bond PRO1.27.C PRO1.28.N

# Save vacuum files
savepdb PRO1 1SP2_vacuum.pdb
saveamberparm PRO1 1SP2_vacuum.prmtop 1SP2_vacuum.inpcrd

# Solvate the system
solvateoct PRO1 TIP3PBOX 10.0
check PRO1 charge
addions PRO1 Cl- 0.
addions PRO1 Na+ 0.

# Save solvated files
saveamberparm PRO1 1SP2_solvated.prmtop 1SP2_solvated.inpcrd
savepdb PRO1 1SP2_solvated.pdb
quit

Notes

Ensure the frcmod and mol2 files for your metal-containing residues are correctly generated using easyPARM.
Load your metalloprotein frcmod file before loading the protein force field ff19SB to ensure tleap will use the standard force field parameters for standard amino acid residues.
Modify the hybridization section based on the Hybridization_Info.dat file, especially if using option 2 for metalloproteins.
If using COMPLEX.lib, the addAtomTypes section is not needed.
Adjust metal coordination bonds according to the Bond_Info.dat file.
For solvated systems, modify the box dimensions and ion addition steps as needed.