ArticleNucleic acids research2014
Efficient in silico exploration of RNA interhelical conformations using Euler angles and WExplore.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Worth the Weight: Sub-Pocket EXplorer (SubPEx), a Weighted Ensemble Method to Enhance Binding-Pocket Conformational Sampling.Journal of chemical theory and computation · 2023Article
- Worth the weight: Sub-Pocket EXplorer (SubPEx), a weighted-ensemble method to enhance binding-pocket conformational sampling.bioRxiv : the preprint server for biology · 2023Article
- Predicting pathological von Willebrand factor unraveling in elongational flow.Biophysical journal · 2021Article
- A Minimal, Adaptive Binning Scheme for Weighted Ensemble Simulations.The journal of physical chemistry. A · 2021Article
- Wepy: A Flexible Software Framework for Simulating Rare Events with Weighted Ensemble Resampling.ACS omega · 2020Article
- REVO: Resampling of ensembles by variation optimization.The Journal of chemical physics · 2019Article
- Mapping the Ligand Binding Landscape.Biophysical journal · 2018Article
- Increasing the length of poly-pyrimidine bulges broadens RNA conformational ensembles with minimal impact on stacking energetics.RNA (New York, N.Y.) · 2018Article
- Weighted Ensemble Simulation: Review of Methodology, Applications, and Software.Annual review of biophysics · 2017Review
- Path-sampling strategies for simulating rare events in biomolecular systems.Current opinion in structural biology · 2017Review
- Multiple Ligand Unbinding Pathways and Ligand-Induced Destabilization Revealed by WExplore.Biophysical journal · 2017Article
- Coupled folding and binding with 2D Window-Exchange Umbrella Sampling.Journal of computational chemistry · 2016Article
- WESTPA: an interoperable, highly scalable software package for weighted ensemble simulation and analysis.Journal of chemical theory and computation · 2015Article
- 15 Years of molecular simulation of drug-binding kinetics.Expert opinion on drug discoveryReview
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
HIV-1 TAR RNA is a two-helix bulge motif that plays a critical role in HIV viral replication and is an important drug target. However, efforts at designing TAR inhibitors have been challenged by its high degree of structural flexibility, which includes slow large-amplitude reorientations of its helices with respect to one another. Here, we use the recently introduced algorithm WExplore in combination with Euler angles to achieve unprecedented sampling of the TAR conformational ensemble. Our ensemble achieves similar agreement with experimental NMR data when compared with previous TAR computational studies, and is generated at a fraction of the computational cost. It clearly emerges from configuration space network analysis that the intermittent formation of the A22-U40 base pair acts as a reversible switch that enables sampling of interhelical conformations that would otherwise be topologically disallowed. We find that most previously determined ligand-bound structures are found in similar location in the network, and we use a sample-and-select approach to guide the construction of a set of novel conformations which can serve as the basis for future drug development efforts. Collectively, our findings demonstrate the utility of WExplore in combination with suitable order parameters as a method for exploring RNA conformational space.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.