A MMFF94 study of the structure and interactions of ocular solutions containing hyaluronic acid with collagen models

Abstract

Abstract Molecular modelling techniques have been widely used in drug discovery fields for rational drug design and compound screening. They have however not been used extensively to understand the mechanism of action of drugs within the human body. In this computational study we have used molecular mechanics modelling to describe a complicated biochemical system that exists in the human eye and to describe the mechanism of action of hyaluronic acid in hydrating the collagen from which the cornea of the eyes are made of. Our studies include atomistic level details about what kind of interactions water has with hyaluronic acid and collagen and in systems containing both hyaluronic acid and collagen models. We observe that water has a greater binding energy to collagen than to hyaluronic acid and that hyaluronic acid binds to collagen via H-bonding and maintains its ability to become hydrated with water based on energetic considerations of the binding energy of water with these biomolecules. The study demonstrates the mechanism of action of hyaluronic acid hydration in the human eye which can be used as model system to study the hydrating effect of other ocular solutions based on the quantitative determination of the binding energy of water with these biological molecules.