2026-10-12T15:37:45Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34021617 2026-09-29T08:48:47Z category_24205 category_24208 item_type_3 month_year_09_2026

Targeting the Alzheimer's-Linked Protease SPPL2a: A Multistage Virtual Screening and Molecular Dynamics Framework for Identifying Selective Inhibitors over Presenilin-1 Sagnika Dutta (23916897) Translational and applied bioinformatics Bioinformatics and computational biology not elsewhere classified Alzheimer's Molecular dynamics simulation Presenilin-1 Signal peptide-peptidase Virtual screening <p dir="ltr">Targeting the intramembrane aspartyl protease SPPL2a (Signal peptide-peptidase like 2a) offers a compelling strategy in Alzheimer’s disease to clear pathogenic substrates such as TMEM106B without triggering the fatal Notch toxicities of γ-secretase/Presenilin-1 (PS1) inhibition, however, therapeutic development has been hindered by its active site conservation with PS1. To address this, we conducted a multistage virtual screening campaign across 244,574 molecules from three chemical repositories – ZINC15, Enamine REAL, and Aurigene Discovery, prioritizing candidates through progressive docking, MM-GBSA rescoring, and 500 ns all-atom membrane molecular dynamics in a POPC bilayer, unveiling ZINC Top 1 as a potent lead candidate.</p> 2026-09-29T08:48:47Z Dataset Dataset 10.6084/m9.figshare.34021617.v1 https://figshare.com/articles/dataset/Targeting_the_Alzheimer_s-Linked_Protease_SPPL2a_A_Multistage_Virtual_Screening_and_Molecular_Dynamics_Framework_for_Identifying_Selective_Inhibitors_over_Presenilin-1/34021617 CC BY 4.0