Unveiling fructose and glucose binding to human serum albumin: fluorescence measurements and docking, molecular dynamics and quantum biochemistry computations

Abstract

This research examines the interaction between human serum albumin (HSA) and various sugar forms (β-D-fructofuranose (FRC), α-D-glucopyranose (GLC), Keto-D-fructose (FRO), Aldehydo-D-glucose (GLO), and modified Aldehydo-D-glucose (GLOm)) using fluorescent spectroscopy, molecular docking simulations, molecular dynamics, protein conformational clusters (EnGens), molecular fractionation with conjugate caps (MFCC) and quantum biochemistry analysis. We analyze molecular and quantum aspects, uncovering interaction energies between sugar atoms and amino acids. Total interaction energy considers protein fragmentation, energetic decomposition, and interaction energy from a bottom-up perspective. Molecular dynamics reveal that unmodified Aldehydo-D-glucose (GLO) escapes HSA binding sites, explaining gradual glycation. We pioneer studying HSA’s binding mechanism with glucose and fructose in a 1:1 ratio using long molecular dynamics simulations. Results suggest the transitional GLOm form has a higher Sudlow I site propensity than unmodified glucose, crucial for K195 glycation. FRO and GLOm interaction tendencies move toward a deeper FA7 cavity, near its center. This approach effectively elucidates small molecule binding mechanisms, consistent with previous experimental results.

Communicated by Ramaswamy H. Sarma

Disclosure statement

The authors declare that they have no conflicts of interest with the contents of this article.

Additional information

Funding

This work was supported by grants from the following Brazilian agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (contract number 465699/2014-6); This study was also financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) Finance Code 001 (PROEX 88887.711696/2022-00); and Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (FUNCAP).