2012 AMBER Tutorial with Biotin and Streptavidin

For additional Rizzo Lab tutorials see AMBER Tutorials.

In this tutorial, we will learn how to run a molecular dynamics simulation of a protein-ligand complex. We will then post-process that simulation by calculating structural fluctuations (with RMSD) and free energies of binding (MM-GBSA).

I. Introduction

AMBER

Amber - Assisted Model Building with Energy Refinement - is a suite of about multiple programs for perform macromolecular simulations. Amber11, the current version of Amber, includes newly released functionality such as PMEMD, particle mesh Ewald MD and soft-core Thermodynamics Integration MD. For the tutorial, we are using an older version which is AMBER10.

The Amber 10 Manual is the primary resource to get started with Amber10. (Tip: Using Adobe Acrobat to view the file, you can simply search the document for keywords such as the name of a simulation parameter, which saves much time.) In addition, Amber Tools User's Manual serves as another reference while using Amber tools. You can also read the manual for Amber11 on Amber11 and AmberTools Users' Manuals

Here are some programs in Amber

1. LEaP: an preparing program for constructing new or modified systems in Amber. It consists of the functions of prep, link, edit, and parm for earlier version of Amber.
2. ANTECHAMBER: in additional to LEap, this main Antechamber suite program is for preparing input files other than standard nucleic acids and proteins.
3. SANDER: according to the Amber 10 manual, it is 'a basic energy minimizer and molecular dynamics program' that can be used to minimize, equilibrate and sample molecular conformations. And this is the program we mainly use in this tutorial to generate trajectory files of the molecular system.
4. PMEMD: version of SANDER that has improved parallel scaling property and optimized speed.
5. PTRAJ: an analysis program for processing trajectory files. One can use ptraj to rotate, translate the structures, evaluate geometrical features and so on.

There is a mailing list you could sign-up for, as an additional resource.

Biotin and Streptavidin

For information of the Biotin and Streptavidin system, see 2012 DOCK tutorial with Streptavidin.

Organizing Directories

While performing MD simulations, it is convenient to adopt a standard directory structure / naming scheme, so that files are easy to find / identify. For this tutorial, we will use something similar to the following:

~username/AMS536/AMBER-Tutorial/001.CHIMERA.MOL.PREP/  
                                002.ANTE.TLEAP/ 
                                003.SANDER/       
                                004.PTRAJ/
                                005.MMGBSA/

II. Structural Preparation

Preparation in Chimera

Generating Structure Files

mk working directory

001- 002- 003- 004-

prep structure

1DF8.rec.lig.pdb
1DF8.lig.chimera.mol2
1DF8.rec.noH.pdb

Manually Editing Ligand Mol2 File

visual block mode to select a rectangular section of text

1DF8.lig.mol2