On the automatic construction of QM/MM Models for biological photoreceptors: rhodopsins as model systems

The automatic building of quantum mechanical/molecular mechanical models (QM/MM) of rhodopsins has been recently proposed. This is a prototype of an approach that will be expanded to make possible the systematic computational investigation of biological photoreceptors. QM/MM models represent useful tools for biophysical studies and for protein engineering, but have the disadvantage of being time-consuming to construct, error prone and, also, of not being consistently constructed by researchers operating in different laboratories. These basic issues impair the possibility to comparatively study hundreds of photoreceptors of the same family, as typically required in biological or biotechnological studies. Thus, in order to carry out systematic studies of photoreceptors or, more generally, light-responsive proteins, some of the authors have recently developed the Automatic Rhodopsin Modeling (ARM) protocol for the fast generation of combined QM/MM models of photoreceptors formed by a single protein incorporating in its cavity a single chromophore. In this chapter, we review the results of such research effort by revising the building protocol and benchmark studies and by discussing selected applications.