8 Chemical Reactions and Equilibria
8.1 Constant pH
Molecular Dynamics Example - Calculating pKas for titratable
side chains in HEWL
In this tutorial we will learn how to use the AMBER software to perform
molecular dynamics simulations at constant pH (CpHMD), one of the most
important chemical equilibria in biology. Solution pH affects titratable
side chains in proteins (and, on occasion, ribozymes), which can have a
dramatic impact on the function, structure, and stability of large
biomolecules. CpHMD is a method that uses a hybrid molecular dynamics/Monte
Carlo approach to sample conformations and protonation states of various
titratable residues in biomolecules. This method can help capture the
coupling between protein structure and pH.
8.2 Constant pH and Redox
Potential MD example: predicting pH-dependent Eo values
In this tutorial we will explore how to perform constant pH and redox potential
(C(pH,E)MD) simulations in AMBER. This method aims at describing electrochemistry
experiments performed at a fixed value of redox potential and pH. We will perform
simulations for N-acetylmicroperoxidase-8 (NAcMP8) axially connected to a histidine
peptide. This system contains a single heme group and its standard redox potential
(Eo) is experimentally known at pH 7.0. With the use of different
simulations for multiple target pH and redox potential values, we will see that our
methodology correctly describes some fundamental behaviors: the Eo related
to the heme decreases with increases in pH, and the pKa of the
pH-active residues decrease with increases in the redox potential.
8.3 A simple coupled
potential QM/MM/MD simulation.
In most simulations, the classical amber force field is the preferred method
for defining and navigating an energy surface. Since AMBER 9, however, we
have offered the capability to simulate coupled quantum mechanical and
Newtonian mechanical (QM/MM) systems. This tutorial demonstrates how to set
up a simple QM/MM MD simulation of NMA in solution.