14 research outputs found
Urea-induced denaturation of PreQ1-riboswitch
Urea, a polar molecule with a large dipole moment, not only destabilizes the
folded RNA structures, but can also enhance the folding rates of large
ribozymes. Unlike the mechanism of urea-induced unfolding of proteins, which is
well understood, the action of urea on RNA has barely been explored. We
performed extensive all atom molecular dynamics (MD) simulations to determine
the molecular underpinnings of urea-induced RNA denaturation. Urea displays its
denaturing power in both secondary and tertiary motifs of the riboswitch (RS)
structure. Our simulations reveal that the denaturation of RNA structures is
mainly driven by the hydrogen bonds and stacking interactions of urea with the
bases. Through detailed studies of the simulation trajectories, we found that
geminate pairs between urea and bases due to hydrogen bonds and stacks persist
only ~ (0.1-1) ns, which suggests that urea-base interaction is highly dynamic.
Most importantly, the early stage of base pair disruption is triggered by
penetration of water molecules into the hydrophobic domain between the RNA
bases. The infiltration of water into the narrow space between base pairs is
critical in increasing the accessibility of urea to transiently disrupted
bases, thus allowing urea to displace inter base hydrogen bonds. This
mechanism, water-induced disruption of base-pairs resulting in the formation of
a "wet" destabilized RNA followed by solvation by urea, is the exact opposite
of the two-stage denaturation of proteins by urea. In the latter case, initial
urea penetration creates a dry-globule, which is subsequently solvated by water
penetration leading to global protein unfolding. Our work shows that the
ability to interact with both water and polar, non-polar components of
nucleotides makes urea a powerful chemical denaturant for nucleic acids.Comment: 41 pages, 18 figure
Urea-Induced Denaturation of PreQ<sub>1</sub>‑Riboswitch
Urea, a polar molecule with a large
dipole moment, not only destabilizes
folded RNA structures but can also enhance the folding rates of large
ribozymes. Unlike the mechanism of urea-induced unfolding of proteins,
which is well understood, the action of urea on RNA has barely been
explored. We performed extensive all-atom molecular dynamics simulations
to determine the molecular underpinnings of urea-induced RNA denaturation.
Urea displays its denaturing power in both secondary and tertiary
motifs of the riboswitch structure. Our simulations reveal that the
denaturation of RNA structures is mainly driven by the hydrogen-bonding
and stacking interactions of urea with the bases. Through detailed
studies of the simulation trajectories, we found that geminate pairs
between urea and bases due to hydrogen bonds and stacks persist only
∼0.1–1 ns, which suggests that the urea–base
interaction is highly dynamic. Most importantly, the early stage of
base-pair disruption is triggered by penetration of water molecules
into the hydrophobic domain between the RNA bases. The infiltration
of water into the narrow space between base pairs is critical in increasing
the accessibility of urea to transiently disrupted bases, thus allowing
urea to displace inter-base hydrogen bonds. This mechanismwater-induced
disruption of base pairs resulting in the formation of a “wet”
destabilized RNA followed by solvation by ureais the exact
opposite of the two-stage denaturation of proteins by urea. In the
latter case, initial urea penetration creates a dry globule, which
is subsequently solvated by water, leading to global protein unfolding.
Our work shows that the ability to interact with both water and polar
or nonpolar components of nucleotides makes urea a powerful chemical
denaturant for nucleic acids
Urea-Induced Denaturation of PreQ<sub>1</sub>‑Riboswitch
Urea, a polar molecule with a large
dipole moment, not only destabilizes
folded RNA structures but can also enhance the folding rates of large
ribozymes. Unlike the mechanism of urea-induced unfolding of proteins,
which is well understood, the action of urea on RNA has barely been
explored. We performed extensive all-atom molecular dynamics simulations
to determine the molecular underpinnings of urea-induced RNA denaturation.
Urea displays its denaturing power in both secondary and tertiary
motifs of the riboswitch structure. Our simulations reveal that the
denaturation of RNA structures is mainly driven by the hydrogen-bonding
and stacking interactions of urea with the bases. Through detailed
studies of the simulation trajectories, we found that geminate pairs
between urea and bases due to hydrogen bonds and stacks persist only
∼0.1–1 ns, which suggests that the urea–base
interaction is highly dynamic. Most importantly, the early stage of
base-pair disruption is triggered by penetration of water molecules
into the hydrophobic domain between the RNA bases. The infiltration
of water into the narrow space between base pairs is critical in increasing
the accessibility of urea to transiently disrupted bases, thus allowing
urea to displace inter-base hydrogen bonds. This mechanismwater-induced
disruption of base pairs resulting in the formation of a “wet”
destabilized RNA followed by solvation by ureais the exact
opposite of the two-stage denaturation of proteins by urea. In the
latter case, initial urea penetration creates a dry globule, which
is subsequently solvated by water, leading to global protein unfolding.
Our work shows that the ability to interact with both water and polar
or nonpolar components of nucleotides makes urea a powerful chemical
denaturant for nucleic acids
Urea-Induced Denaturation of PreQ<sub>1</sub>‑Riboswitch
Urea, a polar molecule with a large
dipole moment, not only destabilizes
folded RNA structures but can also enhance the folding rates of large
ribozymes. Unlike the mechanism of urea-induced unfolding of proteins,
which is well understood, the action of urea on RNA has barely been
explored. We performed extensive all-atom molecular dynamics simulations
to determine the molecular underpinnings of urea-induced RNA denaturation.
Urea displays its denaturing power in both secondary and tertiary
motifs of the riboswitch structure. Our simulations reveal that the
denaturation of RNA structures is mainly driven by the hydrogen-bonding
and stacking interactions of urea with the bases. Through detailed
studies of the simulation trajectories, we found that geminate pairs
between urea and bases due to hydrogen bonds and stacks persist only
∼0.1–1 ns, which suggests that the urea–base
interaction is highly dynamic. Most importantly, the early stage of
base-pair disruption is triggered by penetration of water molecules
into the hydrophobic domain between the RNA bases. The infiltration
of water into the narrow space between base pairs is critical in increasing
the accessibility of urea to transiently disrupted bases, thus allowing
urea to displace inter-base hydrogen bonds. This mechanismwater-induced
disruption of base pairs resulting in the formation of a “wet”
destabilized RNA followed by solvation by ureais the exact
opposite of the two-stage denaturation of proteins by urea. In the
latter case, initial urea penetration creates a dry globule, which
is subsequently solvated by water, leading to global protein unfolding.
Our work shows that the ability to interact with both water and polar
or nonpolar components of nucleotides makes urea a powerful chemical
denaturant for nucleic acids
Urea-Induced Denaturation of PreQ<sub>1</sub>‑Riboswitch
Urea, a polar molecule with a large
dipole moment, not only destabilizes
folded RNA structures but can also enhance the folding rates of large
ribozymes. Unlike the mechanism of urea-induced unfolding of proteins,
which is well understood, the action of urea on RNA has barely been
explored. We performed extensive all-atom molecular dynamics simulations
to determine the molecular underpinnings of urea-induced RNA denaturation.
Urea displays its denaturing power in both secondary and tertiary
motifs of the riboswitch structure. Our simulations reveal that the
denaturation of RNA structures is mainly driven by the hydrogen-bonding
and stacking interactions of urea with the bases. Through detailed
studies of the simulation trajectories, we found that geminate pairs
between urea and bases due to hydrogen bonds and stacks persist only
∼0.1–1 ns, which suggests that the urea–base
interaction is highly dynamic. Most importantly, the early stage of
base-pair disruption is triggered by penetration of water molecules
into the hydrophobic domain between the RNA bases. The infiltration
of water into the narrow space between base pairs is critical in increasing
the accessibility of urea to transiently disrupted bases, thus allowing
urea to displace inter-base hydrogen bonds. This mechanismwater-induced
disruption of base pairs resulting in the formation of a “wet”
destabilized RNA followed by solvation by ureais the exact
opposite of the two-stage denaturation of proteins by urea. In the
latter case, initial urea penetration creates a dry globule, which
is subsequently solvated by water, leading to global protein unfolding.
Our work shows that the ability to interact with both water and polar
or nonpolar components of nucleotides makes urea a powerful chemical
denaturant for nucleic acids
Urea-Induced Denaturation of PreQ<sub>1</sub>‑Riboswitch
Urea, a polar molecule with a large
dipole moment, not only destabilizes
folded RNA structures but can also enhance the folding rates of large
ribozymes. Unlike the mechanism of urea-induced unfolding of proteins,
which is well understood, the action of urea on RNA has barely been
explored. We performed extensive all-atom molecular dynamics simulations
to determine the molecular underpinnings of urea-induced RNA denaturation.
Urea displays its denaturing power in both secondary and tertiary
motifs of the riboswitch structure. Our simulations reveal that the
denaturation of RNA structures is mainly driven by the hydrogen-bonding
and stacking interactions of urea with the bases. Through detailed
studies of the simulation trajectories, we found that geminate pairs
between urea and bases due to hydrogen bonds and stacks persist only
∼0.1–1 ns, which suggests that the urea–base
interaction is highly dynamic. Most importantly, the early stage of
base-pair disruption is triggered by penetration of water molecules
into the hydrophobic domain between the RNA bases. The infiltration
of water into the narrow space between base pairs is critical in increasing
the accessibility of urea to transiently disrupted bases, thus allowing
urea to displace inter-base hydrogen bonds. This mechanismwater-induced
disruption of base pairs resulting in the formation of a “wet”
destabilized RNA followed by solvation by ureais the exact
opposite of the two-stage denaturation of proteins by urea. In the
latter case, initial urea penetration creates a dry globule, which
is subsequently solvated by water, leading to global protein unfolding.
Our work shows that the ability to interact with both water and polar
or nonpolar components of nucleotides makes urea a powerful chemical
denaturant for nucleic acids
Urea-Induced Denaturation of PreQ<sub>1</sub>‑Riboswitch
Urea, a polar molecule with a large
dipole moment, not only destabilizes
folded RNA structures but can also enhance the folding rates of large
ribozymes. Unlike the mechanism of urea-induced unfolding of proteins,
which is well understood, the action of urea on RNA has barely been
explored. We performed extensive all-atom molecular dynamics simulations
to determine the molecular underpinnings of urea-induced RNA denaturation.
Urea displays its denaturing power in both secondary and tertiary
motifs of the riboswitch structure. Our simulations reveal that the
denaturation of RNA structures is mainly driven by the hydrogen-bonding
and stacking interactions of urea with the bases. Through detailed
studies of the simulation trajectories, we found that geminate pairs
between urea and bases due to hydrogen bonds and stacks persist only
∼0.1–1 ns, which suggests that the urea–base
interaction is highly dynamic. Most importantly, the early stage of
base-pair disruption is triggered by penetration of water molecules
into the hydrophobic domain between the RNA bases. The infiltration
of water into the narrow space between base pairs is critical in increasing
the accessibility of urea to transiently disrupted bases, thus allowing
urea to displace inter-base hydrogen bonds. This mechanismwater-induced
disruption of base pairs resulting in the formation of a “wet”
destabilized RNA followed by solvation by ureais the exact
opposite of the two-stage denaturation of proteins by urea. In the
latter case, initial urea penetration creates a dry globule, which
is subsequently solvated by water, leading to global protein unfolding.
Our work shows that the ability to interact with both water and polar
or nonpolar components of nucleotides makes urea a powerful chemical
denaturant for nucleic acids