ROTDIF-web and ALTENS: GenApp-based Science Gateways for Biomolecular
Nuclear Magnetic Resonance (NMR) Data Analysis and Structure Modeling
Yuexi Chen1, Cheol Jeong2, Alexey Savelyev2, Susan Krueger3, Joseph E.
Curtis3, Emre H. Brookes2, David Fushman1
1 Department of Chemistry & Biochemistry, University of Maryland, College
Park. MD
2 Department of Chemistry & Biochemistry, University of Montana, Missoula,
MT
3 NIST Center for Neutron Research, National Institute of Standards and
Technology, Gaithersburg, MD
*Abstract*—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.
