Article in Nucleic Acids Research – Web Server Issue (2023)
31 10 2023
The publication in Nucleic Acids Research – Web Server Issue describes the GS-SMD web server (https://gs-smd.biomodellab.eu/) created by Professor Filipek’s research group. This server employs the steered molecular dynamics (SMD) methodology to study behavior of substrates of γ-secretase (a protein complex composed of four membrane proteins) in its active site.
γ-Secretase is a protease that cleaves substrates in the cell membrane environment. There are over 170 known substrates of this enzyme, one of which is APP (Amyloid Precursor Protein), which produces β-amyloid (Aβ), which is the cause of Alzheimer’s disease. The GS-SMD server also allows introduction of mutations, both to the enzyme and the substrate, to study their impact on unfolding the substrate helix in the active site and on the substrate trimming mechanism, leading to formation of various products, e.g. Aβ42, which is a main component of amyloid plaques formed in neurodegenerative diseases.
U. Orzeł, P. Pasznik, P. Miszta, M. Lorkowski, S. Niewieczerzał, J. Jakowiecki, S. Filipek. GS-SMD server for steered molecular dynamics of peptide substrates in the active site of the γ-secretase complex. Nucleic Acids Research (2023) 51, W251-W262.
Link: https://academic.oup.com/nar/article/51/W1/W251/7173862
