From in silico docking to in vivo relevance: Predicting drug binding to ligand-bound human serum albumin

Binding of drugs to plasma proteins plays a critical role in determining pharmacokinetics, bioavailability, and therapeutic efficacy. Among plasma proteins, Human Serum Albumin is the primary carrier responsible for transporting a wide range of endogenous compounds and pharmaceutical agents in circulation. However, in vivo conditions often involve albumin already bound to endogenous ligands such as fatty acids, bilirubin, or other drugs, which can alter the availability and affinity of binding sites. This lecture explores the application of molecular docking as a computational tool to predict drug binding behavior in ligand-occupied albumin systems. By modeling drug interactions with ligand-bound conformations of human serum albumin, docking studies can provide insights into competitive binding, site displacement, and potential drug–drug interactions. Such in silico approaches offer a rapid and cost-effective strategy to complement experimental binding studies and improve the prediction of pharmacologically relevant interactions. Integrating molecular docking with pharmacokinetic knowledge can enhance our understanding of drug distribution under physiologically realistic conditions.