Computational Investigation of Glucose Binding Receptor

Abstract

The rapid rise in diabetes patients worldwide demands new diabetes diagnostics and therapeutics. Targeting glucose in the human body could be the future insulin alternative therapy. However, glucose recognition in an aqueous solution is a challenging task. The hydroxyl groups present on glucose molecules resemble hydroxyl groups present on water molecules and hide in the solvent, making it challenging to distinguish hydroxyl groups of glucose from water. Even the natural carbohydrate-binding proteins such as Lectins have a low affinity towards glucose. All though glucose recognition in water is not impossible. Several proteins and boronic acid-based receptors are developed for glucose sensing. The structural instability of proteins in abnormal environmental conditions and low affinity of boronic acid receptors forced the search for glucose selective synthetic receptors. Professor Anthony Davis and his team from the University of Bristol developed a glucose selective synthetic receptor by using three [2-(Carbamoylamino)phenyl]urea pillars as polar fragments and a pair of triethyl-mesitylene as an apolar fragment. The receptor is developed based on temple architecture that can encapsulate the glucose molecule in its cage binding through a series of hydrogen bonding and CH-and#960; interactions with high affinity in a solvent using the rational method. However, rational molecular designing is slow and limited to human ideas. Therefore, high-throughput virtual screening has been carried out in this work to identify the glucose binding fragments from the ZINC compound database using the GLIDE program. Ideal fragments are selected based on the glide score. Further, the binding affinity of the glucose-compound complexes was calculated using the MM-GBSA method. Nevertheless,