Abstract
Aptamer has been long studied as a substitute of antibodies for many purposes. However, due to the exceeded length of the aptamers obtained in vitro, difficulties arise in its manipulation during its molecular conjugation on the matrix surfaces. Current study focuses on computational improvement for aptamers screening of hepatitis B surface antigen (HBsAg) through optimization of the length sequences obtained from SELEX. Three original aptamers with affinity against HBsAg were truncated into five short hairpin structured aptamers and their affinity against HBsAg was thoroughly studied by molecular docking, molecular dynamics (MD) simulation, and Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) method. The result shows that truncated aptamers binding on HBsAg “a” determinant region are stabilized by the dynamic H-bond formation between the active binding residues and nucleotides. Amino acids residues with the highest hydrogen bonds hydrogen bond interactions with all five aptamers were determined as the active binding residues and further characterized. The computational prediction of complexes binding will include validations through experimental assays in future studies. Current study will improve the current in vitro aptamers by minimizing the aptamer length for its easy manipulation.
Highlights
Hepatitis B is a potentially life-threatening disease which majorly affects the liver, caused by the hepatitis B virus
The thorough approach in determining the suitable aptamers against hepatitis B surface antigen (HBsAg) by combining a multiple assessing strategies will tremendously improve the effort of aptamer screening
By designing the three-dimensional structure of proteins and aptamers de novo, process of aptamers sequences selection against HBsAg can begin with the computational chemistry approach on a reasonable computational cost before expanding the study in the lab
Summary
Hepatitis B is a potentially life-threatening disease which majorly affects the liver, caused by the hepatitis B virus. Hepatitis B virion consists of outer lipid envelope and an icosahedral nucleocapsid core composed of protein (HBcAg) [2]. The outer envelope contains embedded proteins which are involved in viral binding of and entry into the susceptible cells (HBsAg) [3]. Surface and core proteins of hepatitis B virus consist of molecular recognition patterns that can be detected by the antigen presenting cells such as helper T cells and trigger the production of the antibodies through B cells. HBsAg is highly recognized by the antigen presenting cells and exists in several subtypes identified by its three determinants: a, d, and y [4].
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