2012 AMBER Tutorial with Biotin and Streptavidin

From Rizzo_Lab
Revision as of 10:46, 28 February 2012 by Lingling (talk | contribs)
Jump to: navigation, search

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).



AMBER - Assisted Model Building with Energy Refinement - is a suite of about multiple programs for perform macromolecular simulations. Amber11, the current version of Amber, is extremely advanced, powerful and fast. PMEMD, particle mesh Ewald MD (boundary condition treatment / parallelized code) can churn out 314 ps/day of data for the system dihydrofolate reductase (159 residue protein) in TIP3P water (23,558 total atoms). However, because PMEMD lacks the ability to restrain the atoms we need properly, we will be using SANDER to perform most of our simulations.

The Amber 11 Manual is the primary resource to get started with AMBER11. (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.

Keywords for preparatory programs:

LEaP: creates or modifies systems in Amber. It consists of the functions of prep, link, edit, and parm.

ANTECHAMBER: the main Antechamber suite program that helps prepare input files for nucleic acids and proteins for LEaP.

Keywords for simulating programs:

SANDER: according to the Amber 10 manual, it is 'a basic energy minimizer and molecular dynamics program. This program relaxes the structure by iteratively moving the atoms down the energy gradient until a sufficiently low average gradient is obtained. The molecular dynamics portion generates configurations of the system by integrating Newtonian equations of motion. MD will sample more configurational space than minimization, and will allow the structure to cross over small potential energy barriers. Configurations may be saved at regular intervals during the simulation for later analysis, and basic free energy calculations using thermodynamic integration may be performed. More elaborate conformational searching and modeling MD studies can also be carried out using the SANDER module. This allows a variety of constraints to be added to the basic force field, and has been designed especially for the types of calculations involved in NMR structure refinement'.

PMEMD: verison of SANDER that has improved parallel scaling property and optimized speed.

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.