Structural discordance in HIV-1 Vpu from brain isolate alarms amyloid fibril forming behavior- a computational perspective.

摘要: Abstract HIV-1 being the most widespread type worldwide, its accounts for almost 95% of all infections including HIV associated dementia (HAD) that triggers neurological dysfunction and neurodegeneration in patients. The common features with HAD other neurodegenerative diseases are accumulation amyloid plaques, neuronal loss deterioration cognitive abilities, amongst which fibrillation is considered to be a hallmark. success effective therapeutics lies understanding mechanisms leading neurotoxicity. Few viral proteins like gp-120 known involved aggregation enhancement infectivity while comprehending neurotoxic role some still underway. In current study, amyloidogenic potential Vpu protein from brain isolate investigated through computational approaches. propensity derived was assessed by several prediction servers projected region 4–35 amyloidogenic. structure modeled subjected 70 ns molecular dynamics (MD) simulation investigate transformation α-helical conformation predicted aggregate into β-sheet, proposing protein's ability initiate fibril formation central proteins. structural were consistent silico results depicts conformational change 8–28 residues Ala8, Ile9, Val10, Ala19, Ile20 Val21 constitutes β-sheet formation. α-helix/β-sheet discordance reflected study highlighting possible transition isolate.