Web-Based Computational Chemistry Education with CHARMMing III: Reduction Potentials of Electron Transfer Proteins

<div><p>A module for fast determination of reduction potentials, <i>E°</i>, of redox-active proteins has been implemented in the CHARMM INterface and Graphics (CHARMMing) web portal (<a href="http://www.charmming.org" target="_blank">www.charmming.org</a>). The free energy of reduction, which is proportional to <i>E°</i>, is composed of an intrinsic contribution due to the redox site and an environmental contribution due to the protein and solvent. Here, the intrinsic contribution is selected from a library of pre-calculated density functional theory values for each type of redox site and redox couple, while the environmental contribution is calculated from a crystal structure of the protein using Poisson-Boltzmann continuum electrostatics. An accompanying lesson demonstrates a calculation of <i>E°</i>. In this lesson, an ionizable residue in a [4Fe-4S]-protein that causes a pH-dependent <i>E°</i> is identified, and the <i>E°</i> of a mutant that would test the identification is predicted. This demonstration is valuable to both computational chemistry students and researchers interested in predicting sequence determinants of <i>E°</i> for mutagenesis.</p>