51 research outputs found
Noncovalent Interactions of Hydrated DNA and RNA Mapped by 2D-IR Spectroscopy
Biomolecules couple to their aqueous environment through a variety of
noncovalent interactions. Local structures at the surface of DNA and RNA are
frequently determined by hydrogen bonds with water molecules, complemented by
non-specific electrostatic and many-body interactions. Structural fluctuations
of the water shell result in fluctuating Coulomb forces on polar and/or ionic
groups of the biomolecular structure and in a breaking and reformation of
hydrogen bonds. Two-dimensional infrared (2D-IR) spectroscopy of vibrational
modes of DNA and RNA gives insight into local hydration geometries, elementary
molecular dynamics, and the mechanisms behind them. In this chapter, recent
results from 2D-IR spectroscopy of native and artificial DNA and RNA are
presented, together with theoretical calculations of molecular couplings and
molecular dynamics simulations. Backbone vibrations of DNA and RNA are
established as sensitive noninvasive probes of the complex behavior of hydrated
helices. The results reveal the femtosecond fluctuation dynamics of the water
shell, the short-range character of Coulomb interactions, and the strength and
fluctuation amplitudes of interfacial electric fields.Comment: To appear as Chapter 8 of Springer Series in Optical Sciences:
Coherent Multidimensional Spectroscopy -- Editors: Cho, Minhaeng (Ed.), 201
Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: The ZIKAlliance consortium
Background: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. Methods: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmissio
Using Wavelet Analysis To Assist in Identification of Significant Events in Molecular Dynamics Simulations
Long
time scale molecular dynamics (MD) simulations of biological systems
are becoming increasingly commonplace due to the availability of both
large-scale computational resources and significant advances in the
underlying simulation methodologies. Therefore, it is useful to investigate
and develop data mining and analysis techniques to quickly and efficiently
extract the biologically relevant information from the incredible
amount of generated data. Wavelet analysis (WA) is a technique that
can quickly reveal significant motions during an MD simulation. Here,
the application of WA on well-converged long time scale (tens of μs)
simulations of a DNA helix is described. We show how WA combined with
a simple clustering method can be used to identify both the physical
and temporal locations of events with significant motion in MD trajectories.
We also show that WA can not only distinguish and quantify the locations
and time scales of significant motions, but by changing the maximum
time scale of WA a more complete characterization of these motions
can be obtained. This allows motions of different time scales to be
identified or ignored as desired
Computational Assessment of Potassium and Magnesium Ion Binding to a Buried Pocket in GTPase-Associating Center RNA
An
experimentally well-studied model of RNA tertiary structures
is a 58mer rRNA fragment, known as GTPase-associating center (GAC)
RNA, in which a highly negative pocket walled by phosphate oxygen
atoms is stabilized by a chelated cation. Although such deep pockets
with more than one direct phosphate to ion chelation site normally
include magnesium, as shown in one GAC crystal structure, another
GAC crystal structure and solution experiments suggest potassium at
this site. Both crystal structures also depict two magnesium ions
directly bound to the phosphate groups comprising this controversial
pocket. Here, we used classical molecular dynamics simulations as
well as umbrella sampling to investigate the possibility of binding
of potassium versus magnesium inside the pocket and to better characterize
the chelation of one of the binding magnesium ions outside the pocket.
The results support the preference of the pocket to accommodate potassium
rather than magnesium and suggest that one of the closely binding
magnesium ions can only bind at high magnesium concentrations, such
as might be present during crystallization. This work illustrates
the complementary utility of molecular modeling approaches with atomic-level
detail in resolving discrepancies between conflicting experimental
results
A User-Friendly DNA Modeling Software for the Interpretation of Cryo-Electron Microscopy Data.
The structural modeling of a macromolecular machine is like a "Lego" approach that is challenged when blocks, like proteins imported from the Protein Data Bank, are to be assembled with an element adopting a serpentine shape, such as DNA templates. DNA must then be built ex nihilo, but modeling approaches are either not user-friendly or very long and fastidious. In this method chapter we show how to use GraphiteLifeExplorer, a software with a simple graphical user interface that enables the sketching of free forms of DNA, of any length, at the atomic scale, as fast as drawing a line on a sheet of paper. We took as an example the nucleoprotein complex of DNA gyrase, a bacterial topoisomerase whose structure has been determined using cryo-electron microscopy (Cryo-EM). Using GraphiteLifeExplorer, we could model in one go a 155 bp long and twisted DNA duplex that wraps around DNA gyrase in the cryo-EM map, improving the quality and interpretation of the final model compared to the initially published data.journal article2017importe
Oxazinin A, a Pseudodimeric Natural Product of Mixed Biosynthetic Origin from a Filamentous Fungus
A racemic,
prenylated polyketide dimer, oxazinin A (<b>1</b>), was isolated
from a novel filamentous fungus in the class Eurotiomycetes,
and its structure was elucidated spectroscopically. The pentacyclic
structure of oxazinin A (<b>1</b>) is a unique combination of
benzoxazine, isoquinoline, and a pyran ring. Oxazinin A (<b>1</b>) exhibited antimycobacterial activity and modestly antagonized transient
receptor potential (TRP) channels
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