Proteins and nucleic acids participate in essentially every biochemical process in living organisms, and the elucidation of their structure and motions is essential for our understanding how these molecular machines perform their function. Nuclear Magnetic Resonance (NMR) spectroscopy is a powerful versatile technique that provides critical information on the molecular structure and dynamics. Spin-relaxation data are used to determine the overall rotational diffusion and local motions of biological macromolecules, while residual dipolar couplings (RDCs) reveal local and long-range structural architecture of these molecules and their complexes. This information allows researchers to refine structures of proteins and nucleic acids and provides restraints for molecular docking. Several software packages have been developed by NMR researchers in order to tackle the complicated experimental data analysis and structure modeling. However, many of them are offline packages or command-line applications that require users to set up the run time environment and also to possess certain programming skills, which inevitably limits accessibility of this software to a broad scientific community. Here we present new science gateways designed for NMR/structural biology community that address these current limitations in NMR data analysis. Using the GenApp technology for scientific gateways (https://genapp.rocks), we successfully transformed ROTDIF and ALTENS, two offline packages for bio-NMR data analysis, into science gateways that provide advanced computational functionalities, cloud-based data management, and interactive 2D and 3D plotting and visualizations. Furthermore, these gateways are integrated with molecular structure visualization tools (Jmol) and with gateways/engines (SASSIE-web) capable of generating huge computer-simulated structural ensembles of proteins and nucleic acids. This enables researchers to seamlessly incorporate conformational ensembles into the analysis in order to adequately take into account structural heterogeneity and dynamic nature of biological macromolecules. ROTDIF-web offers a versatile set of integrated modules/tools for determining and predicting molecular rotational diffusion tensors and model-free characterization of bond dynamics in biomacromolecules and for docking of molecular complexes driven by the information extracted from NMR relaxation data. ALTENS allows characterization of the molecular alignment under anisotropic conditions, which enables researchers to obtain accurate local and long-range bond-vector restraints for refining 3-D structures of macromolecules and their complexes. We will describe our experience bringing our programs into GenApp and illustrate the use of these gateways for specific examples of protein systems of high biological significance. We expect these gateways to be useful to structural biologists and biophysicists as well as NMR community and to stimulate other researchers to share their scientific software in a similar way.
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Design, optimization and analysis of large DNA and RNA nanostructures through interactive visualization, editing and molecular simulation
Abstract This work seeks to remedy two deficiencies in the current nucleic acid nanotechnology software environment: the lack of both a fast and user-friendly visualization tool and a standard for structural analyses of simulated systems. We introduce here oxView, a web browser-based visualizer that can load structures with over 1 million nucleotides, create videos from simulation trajectories, and allow users to perform basic edits to DNA and RNA designs. We additionally introduce open-source software tools for extracting common structural parameters to characterize large DNA/RNA nanostructures simulated using the coarse-grained modeling tool, oxDNA, which has grown in popularity in recent years and is frequently used to prototype new nucleic acid nanostructural designs, model biophysics of DNA/RNA processes, and rationalize experimental results. The newly introduced software tools facilitate the computational characterization of DNA/RNA designs by providing multiple analysis scripts, including mean structures and structure flexibility characterization, hydrogen bond fraying, and interduplex angles. The output of these tools can be loaded into oxView, allowing users to interact with the simulated structure in a 3D graphical environment and modify the structures to achieve the required properties. We demonstrate these newly developed tools by applying them to design and analysis of a range of DNA/RNA nanostructures.
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- Award ID(s):
- 1931487
- NSF-PAR ID:
- 10168434
- Date Published:
- Journal Name:
- Nucleic Acids Research
- ISSN:
- 0305-1048
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1093/nar/gkaa417
