150 research outputs found
Electrostatics in the Stability and Misfolding of the Prion Protein: Salt Bridges, Self-Energy, and Solvation
Using a recently developed mesoscopic theory of protein dielectrics, we have
calculated the salt bridge energies, total residue electrostatic potential
energies, and transfer energies into a low dielectric amyloid-like phase for 12
species and mutants of the prion protein. Salt bridges and self energies play
key roles in stabilizing secondary and tertiary structural elements of the
prion protein. The total electrostatic potential energy of each residue was
found to be invariably stabilizing. Residues frequently found to be mutated in
familial prion disease were among those with the largest electrostatic
energies. The large barrier to charged group desolvation imposes regional
constraints on involvement of the prion protein in an amyloid aggregate,
resulting in an electrostatic amyloid recruitment profile that favours regions
of sequence between alpha helix 1 and beta strand 2, the middles of helices 2
and 3, and the region N-terminal to alpha helix 1. We found that the
stabilization due to salt bridges is minimal among the proteins studied for
disease-susceptible human mutants of prion protein
Minimal distance transformations between links and polymers: Principles and examples
The calculation of Euclidean distance between points is generalized to
one-dimensional objects such as strings or polymers. Necessary and sufficient
conditions for the minimal transformation between two polymer configurations
are derived. Transformations consist of piecewise rotations and translations
subject to Weierstrass-Erdmann corner conditions. Numerous examples are given
for the special cases of one and two links. The transition to a large number of
links is investigated, where the distance converges to the polymer length times
the mean root square distance (MRSD) between polymer configurations, assuming
curvature and non-crossing constraints can be neglected. Applications of this
metric to protein folding are investigated. Potential applications are also
discussed for structural alignment problems such as pharmacophore
identification, and inverse kinematic problems in motor learning and control.Comment: Submitted to J. Phys.:Condens. Matte
A systematically coarse-grained model for DNA, and its predictions for persistence length, stacking, twist, and chirality
We introduce a coarse-grained model of DNA with bases modeled as rigid-body
ellipsoids to capture their anisotropic stereochemistry. Interaction potentials
are all physicochemical and generated from all-atom simulation/parameterization
with minimal phenomenology. Persistence length, degree of stacking, and twist
are studied by molecular dynamics simulation as functions of temperature, salt
concentration, sequence, interaction potential strength, and local position
along the chain, for both single- and double-stranded DNA where appropriate.
The model of DNA shows several phase transitions and crossover regimes in
addition to dehybridization, including unstacking, untwisting, and collapse
which affect mechanical properties such as rigidity and persistence length. The
model also exhibits chirality with a stable right-handed and metastable
left-handed helix.Comment: 30 pages, 20 figures, Supplementary Material available at
http://www.physics.ubc.ca/~steve/publications.htm
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