Exploring the Binding Affinities of Fructose and Galactose to Human Serum Albumin

Abstract

Human serum albumin (HSA) is the most abundant transport protein found in human blood. It is known to bind a wide range of drugs, metabolites, and nutrients. The glycation of HSA causes abnormal biological effects. Importantly, glycated HSA (GHSA) is of interest as a potential diabetes biomarker. Many biosensor studies successfully used GHSA as a diabetes biomarker. Recently, a crystal structure of glycated HSA has been reported where a glucose dimer were found in a drug-binding site. HSA can also bind fructose and galactose, but no in-depth binding mechanism is available. To explore binding mechanisms of these sugars, we therefore employed molecular dynamics (MD) simulations and residues interaction energy (INT) calculations to obtain microscopic details in comparison to glucose-bound system form a previous work. Our results show that glucose is the most preferrable sugar for HSA. However, comparing between fructose and galactose, HSA prefers fructose to galactose. Being dimer is a key for tight binding. The movements of top domains are also crucial for sugar binding affinities.Furthermore, key interactions that promote the sugar binding are also extracted here. An insight obtained here will play a role in design and development of diabetes biosensor.