Flap Dynamics in Pepsin-Like Aspartic Proteases: A Computational Perspective Using Plasmepsin-II and BACE-1 as Model Systems.

ABSTRACT: The flexibility of β hairpin structure known as the flap plays a key role in catalytic activity and substrate intake in pepsin-like aspartic proteases. Most of these enzymes share structural and sequential similarity. In this study, we have used apo Plm-II and BACE-1 as model systems. In the apo form of the proteases, a conserved tyrosine residue in the flap region remains in a dynamic equilibrium between the normal and flipped states through rotation of the χ₁ and χ₂ angles. Independent MD simulations of Plm-II and BACE-1 remained stuck either in the normal or flipped state. Metadynamics simulations using side-chain torsion angles (χ₁ and χ₂ of tyrosine) as collective variables sampled the transition between the normal and flipped states. Qualit

SUBMITTER: Bhakat S 

PROVIDER: S-EPMC8889585 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature