title: Molecular dynamics and binding specificity analysis of the bovine immunodeficiency virus BIV Tat-TAR complex.
abstract: We have performed molecular dynamics (MD) simulations, with particle-mesh Ewald, explicit waters, and counterions, and binding specificity analyses using combined molecular mechanics and continuum solvent (MM-PBSA) on the bovine immunodeficiency virus (BIV) Tat peptide-TAR RNA complex. The solution structure for the complex was solved independently by Patel and co-workers and Puglisi and co-workers. We investigated the differences in both structures and trajectories, particularly in the formation of the U-A-U base triple, the dynamic flexibility of the Tat peptide, and the interactions at the binding interface. We observed a decrease in RMSD in comparing the final average RNA structures and initial RNA structures of both trajectories, which suggests the convergence of the RNA structures to a MD equilibrated RNA structure. We also calculated the relative binding of different Tat peptide mutants to TAR RNA and found qualitative agreement with experimental studies.
authors.affiliation: Department of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco, California 94143, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Reyes
authors.forename: R
authors.initials: R
authors.lastname: Nifosì
authors.forename: A D
authors.initials: AD
authors.lastname: Frankel
authors.forename: P A
authors.initials: PA
authors.lastname: Kollman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D003198:Computer Simulation; D015696:Gene Products, tat / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016325:HIV Long Terminal Repeat / Q000235:genetics; D006860:Hydrogen Bonding; D016087:Immunodeficiency Virus, Bovine / Q000737:chemistry / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D015696:Gene Products, tat; D010446:Peptide Fragments; D012367:RNA, Viral