Sequence, Structural Analysis and Metrics to Define the Unique Dynamic Features of the Flap Regions Among Aspartic Proteases

Abstract

Aspartic proteases are a class of hydrolytic enzymes that have been implicated in a number of diseases such as HIV, malaria, cancer and Alzheimer's. The flap region of aspartic proteases is a characteristic unique structural feature of these enzymes; and found to have a profound impact on protein overall structure, function and dynamics. Flap dynamics also plays a crucial role in drug binding and drug resistance. Therefore, understanding the structure and dynamic behavior of this flap regions is crucial in the design of potent and selective inhibitors against aspartic proteases. Defining metrics that can describe the flap motion/dynamics has been a challenging topic in literature. This review is the first attempt to compile comprehensive information on sequence, structure, motion and metrics used to assess the dynamics of the flap region of different aspartic proteases in "one pot". We believe that this review would be of critical importance to the researchers from different scientific domains.

Keywords: Aspartic proteases; Flap dynamics; Hydrolytic enzymes; Protein flexibility.