A Structure-Based Model for Predicting Serum Albumin Binding

Abstract

One of the many factors involved in determining the distribution and metabolism of a compound is the strength of its binding to human serum albumin. While experimental and QSAR approaches for determining binding to albumin exist, various factors limit their ability to provide accurate binding affinity for novel compounds. Thus, to complement the existing tools, we have developed a structure-based model of serum albumin binding. Our approach for predicting binding incorporated the inherent flexibility and promiscuity known to exist for albumin. We found that a weighted combination of the predicted logP and docking score most accurately distinguished between binders and nonbinders. This model was successfully used to predict serum albumin binding in a large test set of therapeutics that had experimental binding data.

Recent Advances on the Development of Pharmacotherapeutic Agents on the Basis of Human Serum Albumin

“…In contrast, the major binding forces for subdomain IIIA were entropy-driven, implying the hydrophobic interactions are the main contributing factors for ligands binding to the pocket of IIIA [17,18]. Such interactions with HSA protein will influence the distribution, metabolism and excretion of small molecules in living systems [12,19].…”

Synthesis, characterization and molecular docking of new C,N‐palladacycles containing pyridinium‐derived ligands: DNA and BSA interaction studies and evaluation as anti‐tumor agents

“…They contribute to the control of osmotic blood pressure, and the maintenance of blood pH . The most outstanding property of albumins is their ability to bind reversibly a large variety of ligands . Bovine serum albumin (BSA) has been proved because of its medical importance, stability, unusual binding properties, low cost, wide availability and high homology, and similarity to human serum albumin in sequence and conformation .…”

“…[19] The most outstanding property of albumins is their ability to bind reversibly a large variety of ligands. [20][21][22] Bovine serum albumin (BSA) has been proved because of its medical importance, stability, unusual binding properties, [23] low cost, wide availability and high homology, and similarity to human serum albumin in sequence and conformation. [24] BSA is composed of three homologous α-helices in domains.…”

Dynamic Combinatorial Chemistry: A New Methodology Comes of Age

“…Indeed, in numerous reported examples BSA did not alter the template library as compared to the blank experiment –,. However, because albumins are known to bind and solubilize fatty acids, hemes, hormones, lipophilic xenobiotics, and many other drug‐like molecules, Danieli et al. not surprisingly found that BSA clearly influenced their library compositions .…”

“…Indeed,i nn umerous reported examples BSA did not alter the template library as compared to the blank experiment. [7a, 20c-e, 26g,l, 27a] However,b ecause albumins are known to bind and solubilize fatty acids, hemes, hormones, lipophilic xenobiotics, [34] and many other drug-like molecules, [35] Danieli et al not surprisingly found that BSAc learly influenced their library compositions. [26i] Therefore, we recommend that control experimentsa re performed instead with an inactive version of the target, [26h] or alternatively in the presence of an established, high-affinity inhibitort ob lock the bindings ite of the target [7a, 20b,c,e, 24c, 26a,l, 27a,e] because thesem ore accuratelys imulate the original tdDCC experiment.…”