Applied Computer-Aided Drug Design: Models and Methods

Up-to-Date Developments in Homology Modeling

Author(s): Muhammed Tilahun Muhammed* and Esin Aki-Yalcin

Pp: 116-135 (20)

DOI: 10.2174/9789815179934123010006

* (Excluding Mailing and Handling)

Abstract

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. 

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