title: Correlation of biological activity with computationally derived structural features from transmembrane hetero-dimers of HIV-1 Vpu with host factors.
abstract: Vpu is an 81 amino acid type I integral membrane protein encoded by human immunodeficiency virus type 1 (HIV-1). It is identified to support viral release by potentially forming ion and substrate conducting channels and by modulating the function of host factors. The focus is on the interaction of the transmembrane domains of Vpu with those of host factors using a combination of molecular dynamics simulations and docking approach. Binding poses and adopted tilt angles of the dimers are analyzed and correlated with experimentally derived activity data from literature. Vpu activity is driven by dimerization with the host protein via its alanine rim Ala-8/11/15/19. Tight binding is shown by an almost parallel alignment of the helices in the dimers. Less parallel alignment is proposed to correlate with lower activity. This article is part of a Special Issue entitled: Viral Membrane Proteins - Channels for Cellular Networking.
authors.affiliation: Institute of Biophotonics, School of Biomedical Science and Engineering, and Biophotonics & Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Li
authors.affiliation: Institute of Biophotonics, School of Biomedical Science and Engineering, and Biophotonics & Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei 112, Taiwan. Electronic address: wfischer@ym.edu.tw.
authors.forename: Wolfgang B
authors.initials: WB
authors.lastname: Fischer
mesh_terms: D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry; D058851:GPI-Linked Proteins / Q000737:chemistry; D015497:HIV-1 / Q000737:chemistry* / Q000378:metabolism; D054298:Human Immunodeficiency Virus Proteins / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry* / Q000502:physiology*; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; D054334:Viral Regulatory and Accessory Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins
keywords: Docking approach; Host factors; Membrane protein; Molecular dynamics simulations; Vpu HIV-1