title: Insights into the structure, correlated motions, and electrostatic properties of two HIV-1 gp120 V3 loops.
abstract: The V3 loop of the glycoprotein 120 (gp120) is a contact point for cell entry of HIV-1 leading to infection. Despite sequence variability and lack of specific structure, the highly flexible V3 loop possesses a well-defined role in recognizing and selecting cell-bound coreceptors CCR5 and CXCR4 through a mechanism of charge complementarity. We have performed two independent molecular dynamics (MD) simulations to gain insights into the dynamic character of two V3 loops with slightly different sequences, but significantly different starting crystallographic structures. We have identified highly populated trajectory-specific salt bridges between oppositely charged stem residues Arg9 and Glu25 or Asp29. The two trajectories share nearly identical correlated motions within the simulations, despite their different overall structures. High occupancy salt bridges play a key role in the major cross-correlated motions in both trajectories, and may be responsible for transient structural stability in preparation for coreceptor binding. In addition, the two V3 loops visit conformations with similarities in spatial distributions of electrostatic potentials, despite their inherent flexibility, which may play a role in coreceptor recognition. It is plausible that cooperativity between overall electrostatic potential, charged residue interactions, and correlated motions could be associated with a coreceptor selection and binding.
authors.affiliation: Department of Bioengineering, University of California Riverside, Riverside, California, United States of America.
authors.forename: Aliana
authors.initials: A
authors.lastname: López de Victoria
authors.forename: Phanourios
authors.initials: P
authors.lastname: Tamamis
authors.forename: Chris A
authors.initials: CA
authors.lastname: Kieslich
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Morikis
mesh_terms: D000595:Amino Acid Sequence; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000737:chemistry / Q000378:metabolism; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments; D019718:Receptors, CXCR4; C514793:gp120 protein, Human immunodeficiency virus 1