title: Inter-helical conformational preferences of HIV-1 TAR-RNA from maximum occurrence analysis of NMR data and molecular dynamics simulations.
abstract: Detecting conformational heterogeneity in biological macromolecules is a key for the understanding of their biological function. We here provide a comparison between two independent approaches to assess conformational heterogeneity: molecular dynamics simulations, performed without inclusion of any experimental data, and maximum occurrence (MaxOcc) distribution over the topologically available conformational space. The latter only reflects the extent of the averaging and identifies regions which are most compliant with the experimentally measured NMR Residual Dipolar Couplings (RDCs). The analysis was performed for the HIV-1 TAR RNA, consisting of two helical domains connected by a flexible bulge junction, for which four sets of RDCs were available as well as an 8.2 μs all-atom molecular dynamics simulation. A sample and select approach was previously applied to extract from the molecular dynamics trajectory conformational ensembles in agreement with the four sets of RDCs. The MaxOcc analysis performed here identifies the most likely sampled region in the conformational space of the system which, strikingly, overlaps well with the structures independently sampled in the molecular dynamics calculations and even better with the RDC selected ensemble.
authors.affiliation: Magnetic Resonance Center "CERM", University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino (FI), Italy. parigi@cerm.unifi.it.
authors.forename: Witold
authors.initials: W
authors.lastname: Andrałojć
authors.affiliation: Magnetic Resonance Center "CERM", University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino (FI), Italy. parigi@cerm.unifi.it and Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Ravera
authors.affiliation: Department of Molecular, Cellular and Developmental Biology and Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Loïc
authors.initials: L
authors.lastname: Salmon
authors.affiliation: Magnetic Resonance Center "CERM", University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino (FI), Italy. parigi@cerm.unifi.it and Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Parigi
authors.affiliation: Department of Biochemistry and Department of Chemistry, Duke University School of Medicine, 307 Research Drive, Durham, North Carolina 27710, USA.
authors.forename: Hashim M
authors.initials: HM
authors.lastname: Al-Hashimi
authors.affiliation: Magnetic Resonance Center "CERM", University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino (FI), Italy. parigi@cerm.unifi.it and Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchinat
mesh_terms: D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D012367:RNA, Viral / Q000737:chemistry*; D020218:Response Elements; D015533:Transcriptional Activation
chemical_list: D012367:RNA, Viral