Comparative Molecular Dynamics Study of E- and Z-Biliverdin-IXα Binding to Human Serum Albumin

Igor V. Polyakov; Maria G. Khrenova

doi:10.14529/jsfi260104

Authors

Igor V. Polyakov Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation https://orcid.org/0000-0001-5459-6709
Maria G. Khrenova Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation https://orcid.org/0000-0001-7117-3089

DOI:

https://doi.org/10.14529/jsfi260104

Keywords:

albumin, biliverdin, bilirubin, molecular dynamics, clustering

Abstract

Human serum albumin (HSA) is the main transporter of a wide range of endogenous ligands, including linear tetrapyrrolic bile pigments. Despite many experimental and theoretical studies, the detailed binding modes of linear tetrapyrroles in HSA remain not fully understood. Here, we investigate the interaction of 4Z,15E and 4Z,15Z biliverdin-IXα with HSA by classical molecular dynamics and machine learning. Starting from the crystallographic complex of HSA with 4Z,15E bilirubin-IXα, we construct models for both biliverdin isomers and explore their conformational space in the initial binding site. We analyse protein-ligand contacts, conformational flexibility, and the populations of distinct binding poses using clustering of interaction fingerprints. The results reveal both shared and isomer-specific interaction patterns between biliverdin and HSA. Several conserved contacts are maintained in both complexes, while distinct differences in contact occupancies and binding pocket conformations are observed between the E- and Z-isomers. Overall, this study provides a consistent molecular level picture of how biliverdin isomers interact with HSA and demonstrates a practical workflow for analysing flexible protein-ligand complexes by combining molecular dynamics with interaction fingerprint clustering.

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