AMBER TI Tutorials
A simple TIMD tutorial about T4-lysozyme
Introduction to TIMD
This is a TIMD tutorial based on the tutorial written by Thomas Steinbrecher. But some important changes have been made to suit the current AMBER 10 version according to Miranda's tutorial from Simmerling's lab.
In this tutorial, free energy calculations will be used to calculate the relative binding free energy of two simple ligands, benzene and phenol to the T4-lysozyme mutant L99A. Free energies will be computed by using the thermodynamic integration facilities of the sander program. A modified van-der-Waals equation (softcore potentials) are used to ensure smooth free energy curves.
Thermodynamic cycle and Method
TI calculations compute the free energy difference between two states A and B by coupling them via a parameters λ that serves as an additional, nonspatial coordinate. This λ formalism allows the free energy difference between the states to be computed as:
Setup of the T4 System
Generation of ligands files
Generate Start Structures
Setup and run MD
After running the simulations on the seawulf cluster, you still have plenty of work to do. The analyze of the data is not so straight and you need to write linux scripts using python or perl to extract the data.