2024 AMBER tutorial 2 with PDBID 1NDV

Introduction

DOCK6 is a great tool that helps us understand ligand binding poses and relative binding energies. When DOCK6 is combined with another computational method known as molecular dynamics, we can calculate free energies of binding and probe how the ligand behaves in the binding pocket. In this tutorial we will walk through the use of AMBER16 to perform and analyze molecular dynamic simulations of PDBID 1NDV.

Getting Started

Before starting simulations it is important to create our directories so that we can keep our simulations organized. Create the following directories:

000.paramters
001.tleap_build
002.equilbration
003.production
004.analysis
zzz.master

We will use the zzz.master directory to store our initial mol2 files and other files we may use that do not belong in another directory. Once you have your directories created you can begin to prepare they system for simulation.

Before Simulation

Structure

We will need mol2 and pdb files of the ligand and receptor separately for these simulations. If you followed the 1NDV DOCK6 VS tutorial you will already have these files and can move them to the zzz.master directory. If you did not follow that tutorial the steps will be listed below, but please refer to it if you require a more in depth tutorial. Please note that the receptor file should be without charges and hydrogens, while the ligand will need the charges and hydrogens.

We will start by generating our receptor file. Open the PDB of 1NDV in Chimera and follow these steps.

1) Select an atom on the receptor and use the entire up arrow until the entire protein is selected
2) Select -> Invert (all models)
3) Actions -> Atoms/Bonds -> delete

This should leave us with just the receptor atoms. Save this as a mol2 file and a pdb file as "1ndv_protein_noH_noCharge" DO NOT add charges or hydrogens.

We will now create the ligand file in a similar fashion.

1) Select an atom on the ligand and use the entire up arrow until the entire protein is selected
2) Select -> Invert (all models)
3) Actions -> Atoms/Bonds -> delete

Before we use this file we must add hydrogens and charges.

To add Hydrogens: Tools -> Structure Editing -> Add Hydrogens
To add Charges: Tools -> Structure Editing -> Add Charges (for this ligand we will use an overall charge of 0)

Be sure to reference the PDB file to ensure that Chimera adds hydrogens in the correct places. Once charges and hydrogens are added you can save the mol2 and pdb files as "1ndv_ligand_addH_addCharge" Place both of these files in the zzz.master directory.