Fatty acid binding to serum albumin: Molecular simulation approaches

• Published in: Biochimica et biophysica acta Vol. 1830; no. 12; pp. 5427 - 5434
• Main Authors: Fujiwara, Shin-ichi, Amisaki, Takashi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2013
• Subjects: binding capacity; blood; Docking; energy; Fatty acid; fatty acids; Fatty Acids - chemistry; Fatty Acids - metabolism; Free energy; Human serum albumin; ligands; Molecular dynamics; Molecular Dynamics Simulation; Serum Albumin - chemistry; Serum Albumin - metabolism; Simulation; Structure-Activity Relationship; structure-activity relationships; warfarin; Molecular dynamics; Human serum albumin; Docking; Simulation; Fatty acid; Free energy
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2013.03.032

Binding affinity for human serum albumin (HSA) is one of the most important factors affecting the distribution and free blood concentration of many ligands. The effect of fatty acids (FAs) on HSA-ligand binding has long been studied. Since the elucidation of the 3-dimensional structure of HSA, molecular simulation approaches have been applied to studies of the structure–function relationship of HSA–FA binding. We review current insights into the effects of FA binding on HSA, focusing on the biophysical insights obtained using molecular simulation approaches such as docking, molecular dynamics (MD), and binding free energy calculations. Possible conformational changes on binding of FA molecules to HSA have been observed through MD simulations. High- and low-affinity FA-binding sites on HSA have been identified based on binding free energy calculations. The relationship between the warfarin binding affinity of HSA and FA molecules has been clarified based on the results of simulations of multi-site FA binding that cannot be experimentally observed. Molecular simulation approaches have great potentials to provide detailed biophysical insights into HSA as well as the effects of the binding of FAs or other ligands to HSA. This article is part of a Special Issue entitled Serum Albumin. •Binding of FA molecules to HSA can modulate ligand binding affinity to HSA.•Molecular simulation approaches have been applied to structural analyses of HSA.•Possible conformational changes of HSA–FA binding were analyzed by MD simulations.•Binding free energy calculations identified high/low affinity FA-binding sites.•Molecular simulation analyzes conditions that cannot be experimentally observed.