Amber Workshop - tutorial 2

(Note: These tutorials are meant to provide illustrative examples of how to use the AMBER software suite to carry out simulations that can be run on a simple workstation in a reasonable period of time. They do not necessarily provide the optimal choice of parameters or methods for the particular application area.)
Copyright Ross Walker 2006

TUTORIAL 2

Using dynamics simulations to estimate binding energetics

By Ross Walker

The purpose of this tutorial is to begin thinking about how one might estimate energetics of binding. In this tutorial we will use the Sander module of Amber 8 to carry out short molecular dynamics simulations of the WW domain from Yes-associated protein (Yap). Structures for this protein have been reported in complex with a bound proline rich peptide and the structure is available from the Brookhaven protein data bank as PDB ID 1JMQ.

We will obtain an estimate of the strength of the binding in this complex by running short MD simulations of the complex, the peptide and the protein. The difference in the average energies will give us a value that we can use as a comparative strength of binding. In this way we can actually monitor the dynamics of both the ligand and protein. This is important since the system dynamics could potentially influence the binding affinity. Note, in this tutorial the length of MD will be very short since this is just for demonstration purposes. In order to obtain accurate results it is necessary to ensure that your system has converged by running long equilibration runs and monitoring the energy. It is also necessary to run a much longer "production" run in order to obtain statistically significant results.

This tutorial consists of three sections:

section1.htm : Create the necessary topology and coordinate files.
section2.htm : Minimize and equilibrate our systems.
section3.htm : Run production MD and estimate the binding energy.

CLICK HERE TO GO TO SECTION 1