Homology Modeling: an Overview of Fundamentals and Tools

Resolving the three dimensional structure of a protein is a critical step in modern drug discovery today. Homology modeling is a powerful tool that can efficiently predict protein structures from their amino acid sequence. Although it might sound simple enough, homology modeling, in fact, has to pass through several sophisticated steps before it can predict an accurate structure of a protein. These steps include template identification, alignment with the template, model construction and many post-modeling processes. Here, we describe in details these different steps, discuss the strengths and limitations of the methods and list a number of successful homology modelling applications in the literature. The objective of this review is to shed light on this extremely useful tool and highlight many case studies in this area of active research.