Web-based computational chemistry education with CHARMMing III: Reduction potentials of electron transfer proteins

• Published in: PLoS computational biology 2014-07, Vol.10 (7), p.e1003739
• Main Authors: Perrin, Jr, B Scott, Miller, Benjamin T, Schalk, Vinushka, Woodcock, H Lee, Brooks, Bernard R, Ichiye, Toshiko
• Format: Article
• Language: English
• Subjects: Biology and Life Sciences; Chemistry; Computational Biology - education; Computational Biology - methods; Computational chemistry; Crystal structure; Education; Educational aspects; Educational technology; Electron Transport; Internet; Libraries; Management; Mutation; Oxidation-Reduction; Physical Sciences; Proteins; Proteins - chemistry; Proteins - metabolism; Studies; Study and teaching; Thermodynamics; Web sites
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1003739

A module for fast determination of reduction potentials, E°, 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°, 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°. In this lesson, an ionizable residue in a [4Fe-4S]-protein that causes a pH-dependent E° is identified, and the E° 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° for mutagenesis.