Quality Assessment of Selected Protein Structures Derived from Homology Modeling and AlphaFold.

Abstract

With technology advancing, many prediction algorithms have been developed to facilitate the modeling of inherently dynamic and flexible macromolecules such as proteins. Improvements in the prediction of protein structures have attracted a great deal of attention due to the advantages they offer, e.g., in drug design. While trusted experimental methods, such as X-ray crystallography, NMR spectroscopy, and electron microscopy, are preferred structure analysis techniques, in silico approaches are also being widely used. Two computational methods, which are on opposite ends of the spectrum with respect to their modus operandi, i.e., homology modeling and AlphaFold, have been established to provide high-quality structures. Here, a comparative study of the quality of structures either predicted by homology modeling or by AlphaFold is presented based on the characteristics determined by experimental studies using structure validation servers to fulfill the purpose. Although AlphaFold is able to predict high-quality structures, high-confidence parts are sometimes observed to be in disagreement with experimental data. On the other hand, while the structures obtained from homology modeling are successful in incorporating all aspects of the experimental structure used as a template, this method may struggle to accurately model a structure in the absence of a suitable template. In general, although both methods produce high-quality models, the criteria by which they are superior to each other are different and thus discussed in detail.