Implications of sequence conservation patterns of serpin B family leading to structural and functional importance

Abstract

SERine Proteinase INhibitors Clade B: SERPINS, a largely dispersed family of protease inhibitors that exhibit a conformational alteration to inhibit target enzymes. Atypical serpin proteins often form aggregates that can accumulate to toxic levels within cells. SerpinB4 is a chymotrypsin-like serine proteinase inhibitor. Phylogenetic analysis of Serpin Clade B revealed no duplication throughout the mammalian clades. Thus, elucidating retention of a single copy of human serpin members in nature, endorsing its essentiality as an inhibitor. Epidemiological studies specify that a rising number of patients are inclined to develop chronic liver disease due to SerpinB4 overexpression. This upregulation is therefore not in fine fettle for the human physiology. Molecular docking protocol classified compound 57, a novel inhibitory compound, as the ligand, best able to fit the binding pocket with a Gold Score of 94. A two hundred nanosecond molecular dynamics simulation of docked SerpinB4 illustrated a steady binding pattern of ligand in the protein's active site. Pursuing this, trajectory analysis was implemented to assess various characteristics of the docked system in terms of function of time. These findings may act effectively in designing effective remedies against SerpinB4.