title: Coevolution Analysis of HIV-1 Envelope Glycoprotein Complex.
abstract: The HIV-1 Env spike is the main protein complex that facilitates HIV-1 entry into CD4+ host cells. HIV-1 entry is a multistep process that is not yet completely understood. This process involves several protein-protein interactions between HIV-1 Env and a variety of host cell receptors along with many conformational changes within the spike. HIV-1 Env developed due to high mutation rates and plasticity escape strategies from immense immune pressure and entry inhibitors. We applied a coevolution and residue-residue contact detecting method to identify coevolution patterns within HIV-1 Env protein sequences representing all group M subtypes. We identified 424 coevolving residue pairs within HIV-1 Env. The majority of predicted pairs are residue-residue contacts and are proximal in 3D structure. Furthermore, many of the detected pairs have functional implications due to contributions in either CD4 or coreceptor binding, or variable loop, gp120-gp41, and interdomain interactions. This study provides a new dimension of information in HIV research. The identified residue couplings may not only be important in assisting gp120 and gp41 coordinate structure prediction, but also in designing new and effective entry inhibitors that incorporate mutation patterns of HIV-1 Env.
authors.affiliation: Computational Sciences and Engineering Center, Qatar Computing Research Institute, Hamad Bin Khalifa University, Doha, Qatar.
authors.forename: Reda
authors.initials: R
authors.lastname: Rawi
authors.affiliation: Computational Sciences and Engineering Center, Qatar Computing Research Institute, Hamad Bin Khalifa University, Doha, Qatar.
authors.forename: Khalid
authors.initials: K
authors.lastname: Kunji
authors.affiliation: King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, National Guards Health Affairs, Riyadh, KSA.  2, Department of Genetics and Genomics, Boston Children’s Hospital, Harvard Medical School, USA.|King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
authors.forename: Abdelali
authors.initials: A
authors.lastname: Haoudi
authors.affiliation: Computational Sciences and Engineering Center, Qatar Computing Research Institute, Hamad Bin Khalifa University, Doha, Qatar.
authors.forename: Halima
authors.initials: H
authors.lastname: Bensmail
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D015704:CD4 Antigens / Q000378:metabolism; D019143:Evolution, Molecular; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics*; D015497:HIV-1 / Q000378:metabolism*; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D053586:Virus Internalization; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics*
chemical_list: D000596:Amino Acids; D015704:CD4 Antigens; D006023:Glycoproteins; D054299:env Gene Products, Human Immunodeficiency Virus