Homology modeling is used to predict protein 3D structure from its amino
acid sequence. It is the most accurate computational approach to estimate 3D
structures. It has straightforward steps that save time and labor. There are several
homology modeling tools under use. There is no sole tool that is superior in every
aspect. Hence, the user should select the most appropriate one carefully. It is also a
common practice to use two or more tools at a time and choose the best model among
the resulting models.
Homology modeling has various applications in the drug design and development
process. Such applications need high-quality 3D structures. It is widely used in
combination with other computational methods including molecular docking and
molecular dynamics simulation. Like the other computational methods, it has been
influenced by the involvement of artificial intelligence. In this regard, homology
modeling tools, like AlphaFold, have been introduced. This type of method is expected
to contribute to filling the gap between protein sequence release and 3D structure
determination.
This chapter sheds light on the history, relatively popular tools and steps of homology
modeling. A detailed explanation of MODELLER is also given as a case study
protocol. Furthermore, homology modeling’s application in drug discovery is explained
by exemplifying its role in the fight against the novel Coronavirus. Considering the
new advances in the area, better tools and thus high-quality models are expected.
These, in turn, pave the way for more applications of it.
Keywords: Computer Aided Drug Design, 3D Structure, Drug Discovery, Homology Modeling, Modeller, Molecular Modeling.
