title: Multiscale simulations on conformational dynamics and membrane interactions of the non-structural 2 (NS2) transmembrane domain.
abstract: Hepatitis C virus (HCV) is one of the most crucial global health issues, in which the HCV non-structural protein 2 (NS2), particularly its three transmembrane segments, plays a crucial role in HCV assembly. In this context, multiscale MD simulations have been applied to investigate the preferred orientation of transmembrane domain of NS2 protein (TNS2) in a POPC bilayer, structural stability and characteristic of intramembrane protein-lipid and protein-protein interaction. Our study indicates that NS2 protein adopts three trans-membrane segments with highly stable α-helix structure in a POPC bilayer and a short helical luminal segment. While the first and second TM segment involved in continuous helical domain, the third TM segment is however cleaved into two sub-segments with different tilt angles via a kink at L87G88. Salt bridges K81-E45, R32-PO4 and R43-PO4 are determined as the key factor to stabilize the structure of TM2 and TM3 which consist of charged residues located in the hydrophobic region of the membrane.
authors.affiliation: Department of Chemistry, KU Leuven, Celestijnenlaan 200F, B-3001, Leuven, Belgium.
authors.forename: Huynh Minh
authors.initials: HM
authors.lastname: Hung
authors.affiliation: Department of Chemistry, KU Leuven, Celestijnenlaan 200F, B-3001, Leuven, Belgium.
authors.forename: Tran Dieu
authors.initials: TD
authors.lastname: Hang
authors.affiliation: Department of Chemistry, KU Leuven, Celestijnenlaan 200F, B-3001, Leuven, Belgium. Electronic address: minh.nguyen@kuleuven.be.
authors.forename: Minh Tho
authors.initials: MT
authors.lastname: Nguyen
mesh_terms: D001665:Binding Sites; D008051:Lipid Bilayers / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry / Q000648:ultrastructure; D008956:Models, Chemical; D062105:Molecular Docking Simulation / Q000379:methods*; D010713:Phosphatidylcholines / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D000072417:Protein Domains; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000648:ultrastructure*
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins; C097010:NS2 protein, Hepatitis C virus; D010713:Phosphatidylcholines; D017361:Viral Nonstructural Proteins; C028694:1-palmitoyl-2-oleoylphosphatidylcholine
keywords: HCV; Hepatitis C virus; MD simulation; NS2; Non structure 2; Transmembrane