Charged binding calculations

Authored by Gabriel Rocklin, last updated June 15 2014

Overview

Many thermodynamically interesting processes involve ions changing chemical environment, such as the transfer of an ion from the gas phase to the solvated phase, the protonation of a protein side chain, or the binding of a charged ligand. Free energy simulations of these processes can be done in two ways: (1) both chemical environments can be represented in the same simulated system, such as when a charged ligand is "pulled" from a protein binding site into the bulk solvent, or (2) different simulated systems can be used for different chemical environments, such as when a charged ligand is alchemically removed from its own "free in solution" box and alchemically inserted into the protein binding site in a different simulated system. In both cases, the computed free energies can depend on details of the calculation setup, such as the boundary conditions applied at the edge of the explicit solvent system (periodic, implicit solvent, or vacuum), the size of the periodic unit cell, and even completely arbitrary details of the solvent molecular topology.

ertain what types of artifacts these processes would introduce artifacts due to the net charge of the system, but these artifacts are now reasonably well understood and analytical methods are available to correct for these artifacts.