Copyright (C) Pengfei Li & Kenneth M. Merz Jr. 2015

Modeling Zinc Enzyme System using the 12-6 LJ Nonbonded Model


Here we describe the zinc enzyme system (PDB ID: 4V2Y) as an example for modeling an atomic ion using the 12-6 LJ nonbonded model:

1. Prepare the PDB file (effort: several minutes):

Here is the original PDB: 4V2Y.pdb. There are no hydrogen atoms in the file. tleap will automatically add them in next step. Users can also use webserver H++ to add hydrogen atoms, which is a more accurate way to determine the protonation state of residues, please check the MCPB.py tutorial for more details.

Clean the PDB file:

awk '$1=="ATOM" || $1=="HETATM" || $1=="TER" || $1=="END"' 4V2Y.pdb > 4V2Y_clean.pdb

Get chain A of the PDB file:

awk 'substr($0, 22, 1) == "A"' 4V2Y_clean.pdb > 4V2Y_clean_A.pdb

Delete the ligand in the PDB file:

awk 'substr($0, 18, 3)!="EF2"' 4V2Y_clean_A.pdb > 4V2Y_clean_A_2.pdb

2. Perform the modeling steps using leap (effort: several minutes):

We need to create an input file manually. Here is the input file: Zn_tleap.in.

We are using the TIP3P water model and the compromise (CM) parameter set (we load the frcmod.ionslrcm_cm_tip3p file in the leap input file).

Here is the explanation of the tleap input file:

source leaprc.ff12SB #Source the ff12SB force field
loadoff atomic_ions.lib #Load the library for atomic ions
mol = loadpdb 4V2Y_clean_A_2.pdb #Load the PDB file
loadamberparams frcmod.ionslrcm_cm_spce#Load the frcmod file for divalent metal ions
loadamberparams frcmod.ionsjc_spce #Load the frcmod file for monovalent metal ions
solvatebox mol SPCBOX 8 #Solvate the system using SPC water box
loadamberparams frcmod.spce #Load the frcmod file for SPCE water
addions mol CL 0 #Neutralize the system using Cl- ions
savepdb mol Zn_4V2Y.pdb #Save the pdb file
saveamberparm mol Zn_4V2Y.prmtop Zn_4V2Y.inpcrd #Save the topology and coordiante files
quit #Quit tleap

Here we can perform the command:

tleap -s -f Zn_tleap.in > Zn_tleap.out

You can also use the addions/addions2 command (for example "addions mol ZN 3") if you want to add several Zinc ions to the system before neutralizing it.

Afterwards you can use the generated topology and coordinate files (Zn_4V2Y.prmtop and Zn_4V2Y.inpcrd) to perform molecular dynamics simulations.