Structural and dynamic properties of urinary human serum albumin fragments: a molecular dynamics study

A microalbuminuria level acts as a good index to screen and monitor diabetes and renal failure. However, the urinary albumin loss after sample preservation and storage is the major bottleneck to obtain the accurate microalbuminuria test. Such loss is due to the rapid albumin fragmentation by urinary proteases. Some fragments were suggested to be bioactive biomarkers of diabetes and renal disease, but no structural and dynamical properties of albumin fragments are available. Thus, in this work, the structural and dynamical properties of reported albumin fragments are revealed using molecular dynamics simulations. The properties of nine fragments (F1-F9) discovered recently were studied at the real pH conditions of urine samples (pH 4.5, 7 and 8). The complete loss of secondary structure is found in short fragments (F1-F6), while large-sized polypeptides (F7-F9) can somehow maintain their folds. Especially, F8 (subdomain IIIB) is the most stable fragment. The difference in histidine protonation states has no impact on the structural stability of albumin fragments. The ability of F8 (subdomain IIIB) to maintain its stability and folds suggests it as an alternative albumin biomarker in urine. An insight obtained here will become the fundamental importance for understanding clinical assays for albumin detection, sample stability and peptidomics analysis of urine.Communicated by Ramaswamy H. Sarma.