The structures and proton-coupled behavior of adenine-thymine (A-T) and a modified base pair containing a thymine isostere, adenine-difluorotoluene (A-F), are studied in different solvents by dispersion-corrected density functional theory. The stability of the canonical Watson-Crick base pair and the mismatched pair in various solvents with low and high dielectric constants is analyzed. It is demonstrated that A-F base pairing is favored in solvents with low dielectric constant. The stabilization and conformational changes induced by protonation are also analyzed for the natural as well as the mismatched base pair. DNA sequences capable of changing their sequence conformation on protonation are used in the construction of pH-based molecular switches. An acidic medium has a profound influence in stabilizing the isostere base pair. Such a large gain in stability on protonation leads to an interesting pH-controlled molecular switch, which can be incorporated in a natural DNA tract.
β-Glucosidase (EC 3.2.1.21)
plays an essential role in the
removal of glycosyl residues from disaccharide cellobiose to produce
glucose during the hydrolysis of lignocellulosic biomass. Although
there exist a few β-glucosidase that are tolerant to large concentrations
of glucose, these enzymes are typically prone to glucose inhibition.
Understanding the basis of this inhibition is important for the production
of cheaper biofuels from lignocellulose. In this study, all
-
atom molecular dynamics simulation at different temperatures and
glucose concentrations was used to understand the molecular basis
of glucose inhibition of GH1 β-glucosidase (B8CYA8) from
Halothermothrix orenii
. Our results show that glucose
induces a broadening of the active site tunnel through residues lining
the tunnel and facilitates the accumulation of glucose. In particular,
we observed that glucose accumulates at the tunnel entrance and near
the catalytic sites to block substrate accessibility and inhibit enzyme
activity. The reduction of enzyme activity was also confirmed experimentally
through specific activity measurements in the presence of 0–2.5
M glucose. We also show that the increase in glucose concentrations
leads to a decrease in the number of water molecules inside the tunnel
to affect substrate hydrolysis. Overall, the results help in understanding
the role of residues along the active site tunnel for the engineering
of glucose-tolerant β-glucosidase.
Elucidating the regulation of glucose tolerance through the interaction between the reaction product and 2 active site pocket residues of a β-glucosidase from Halothermothrix orenii
Mammalian and Drosophila Melanogaster model mitochondrial membrane compositions are constructed from experimental lipidomics data. Simplified compositions for inner and outer mitochondrial membranes are provided, including an asymmetric inner mitochondrial membrane. We performed atomistic molecular dynamics simulations of these membranes and computed their material properties. When comparing these properties to those obtained by extrapolation from their constituting lipids, we find good overall agreement. Finally, we analyzed the curvature effect of cardiolipin, considering ion concentration effects, oxidation and pH. We draw the conclusion that cardiolipin negative curvature is most likely due to counterion effects, such as cation adsorption, in particular of H3O+. This oft-neglected effect might account for the puzzling behavior of this lipid.
The
effect of topology
on the structure, self-assembly, and selective Fe3+ binding
of δ-peptides has been investigated. A series of δ-peptides
with an amino acid containing dihydropyrimidinone and o-, m-, and p-aminobenzoic acids
have been designed to study the structure–function relationship.
A new amino acid containing dihydropyrimidinone was synthesized by
the Biginelli reaction of ethyl acetoacetate, urea, and o-nitrobenzaldehyde followed by reduction with iron powder and acetic
acid. X-ray crystallography sheds some light on the conformations,
self-assembly, and the diverse degrees of π–π stacking
of adjacent δ-peptide molecules. Peptides with o- or m-aminobenzoic acid form eight-membered intramolecular
hydrogen-bonded turn conformations and self-assemble through intermolecular
hydrogen bonds between dihydropyrimidinone units to form a butterfly-like
structure. However, the δ-peptide containing p-aminobenzoic acid forms a water-mediated cage-like structure. Irrespective
of the presence of the same functional groups, only the δ-peptide
with o-aminobenzoic acid can selectively bind Fe3+ in methanol as well as in water. The topology plays a crucial
role in the selective Fe3+ ion binding by the δ-peptide.
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