Web-Based Computational Chemistry Education with CHARMMing III: Reduction Potentials of Electron Transfer Proteins: e1003739

A module for fast determination of reduction potentials, E degree , of redox-active proteins has been implemented in the CHARMM INterface and Graphics (CHARMMing) web portal (www.charmming.org). The free energy of reduction, which is proportional to E degree , 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 E degree . In this lesson, an ionizable residue in a [4Fe-4S]-protein that causes a pH-dependent E degree is identified, and the E degree 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 E degree for mutagenesis.