Inter-helical conformational preferences of HIV-1 TAR-RNA from maximum occurrence analysis of NMR data and molecular dynamics simulations.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Andrałojć, W; Ravera, E; Salmon, L; Parigi, G; Al-Hashimi, HM; Luchinat, C

Published Date

  • February 17, 2016

Published In

Volume / Issue

  • 18 / 8

Start / End Page

  • 5743 - 5752

PubMed ID

  • 26360616

Pubmed Central ID

  • PMC6589165

Electronic International Standard Serial Number (EISSN)

  • 1463-9084

Digital Object Identifier (DOI)

  • 10.1039/c5cp03993b


  • eng

Conference Location

  • England