Lab 2

Binding free energies

Nathan Baker

Washington University in St. Louis
Department of Biochemistry and Molecular Biophysics
Center for Computational Biology

Table of Contents
Introduction
Acknowledgments
"Single-point" implicit solvent binding energies
Parameterization
Calculating electrostatic solvation energies
Calculating electrostatic binding energies
Energies by thermodynamic integration
Preparing the Na+-ether complex
Loading the parameters and starting structure
Fixing the starting structure
Adding the Na+
Specifying the perturbation
Solvate
Save your work
Minimization
Thermodynamic integration
λ = 0
λ = 0.25
λ = 0.5, 0.75, 1.00
Performing the integration
MM/PBSA binding energy calculations
Running the trajectories
Na+-bound trajectory
K+-bound trajectory
Molecular mechanics trajectory analysis
Quasi-harmonic entropy analysis
Energy analysis
Solvation energies
Nonpolar energies
Polar energies
Putting it all together