Comparison of computational models for simulating heme proteins: A study of cytochrome C peroxidase

Abstract

We have investigated four computational models of the resting state and HOOH-bound complex of a heme protein, cytochrome c peroxidase (CCP), to determine the most efficient methodology that yields reliable results. Previous studies have focused on the overall dynamic structure of proteins and not explicitly on the motion of small molecules and their effect on nearby residues. In this study, the effects of dielectric, boundary constraints, explicit inclusion of solvent, and charges on the heme unit have specifically been examined. For the case studied here, in which interactions with water are very important, it was found that, contrary to commonly accepted procedures, a distance-dependent dielectric (e = 4R) with a constrained protein and no solvent resulted in unacceptably large deviations from more accurate models. In this case, even a buried Trp residue hydrogen bonded to the water network showed large deviations due to the exaggerated motions of the waters. However, use of a constant dielectric (e = 1) with the same constraints resulted in a computationally efficient model that yielded properties very similar to the more accurate models. © 1992 John Wiley & Sons, Inc.