title: Comparative analysis of HIV-1 Tat variants.
abstract: HIV-1 Tat protein is a crucial element for viral replication; therefore, its inhibition might be exploited against the AIDS infection. To gain insights on the natural variability of this protein, we present a comparative investigation on the relationship between the primary sequences and the experimentally available three-dimensional structures from the HIV-1 Tat variants Z2, BRU, and MAL. Our computational tools include sequence conservation algorithms, structural analysis, electrostatic modeling, and molecular dynamics (MD) simulations. We find that two regions located between residues 10-18 and 41-52 display the highest primary sequence conservation, while the most conserved region among the available structures corresponds approximately to the segment between positions approximately 44 and 50. Furthermore, in spite of their large structural divergence, Tat variants share a common mode for long-range intramolecular interactions. Finally, the flexibility of the Z2, BRU, and MAL variants, as emerging from multinanosecond MD simulations, is rather similar. Based on this work, we conclude that the turnlike region between amino acids 44 and 50 is structurally most conserved, emerging as an important motif for pharmaceutical targeting aimed toward inhibiting Tat action.
authors.affiliation: International School for Advanced Studies and INFM-DEMOCRITOS Modeling Center for Research in Atomistic Simulation, Trieste, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Pantano
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni
mesh_terms: D000465:Algorithms; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods*; D017124:Conserved Sequence; D004279:DNA, Viral; D015696:Gene Products, tat / Q000737:chemistry*; D015756:Genes, tat; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015233:Models, Statistical; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry; D040901:Proteomics / Q000379:methods*; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D013329:Structure-Activity Relationship; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D004279:DNA, Viral; D015696:Gene Products, tat; D011506:Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus