7,663 research outputs found
J-factors of short DNA molecules
The propensity of short DNA sequences to convert to the circular form is
studied by a mesoscopic Hamiltonian method which incorporates both the bending
of the molecule axis and the intrinsic twist of the DNA strands. The base pair
fluctuations with respect to the helix diameter are treated as path
trajectories in the imaginary time path integral formalism. The partition
function for the sub-ensemble of closed molecules is computed by imposing chain
ends boundary conditions both on the radial fluctuations and on the angular
degrees of freedom. The cyclization probability, the J-factor, proves to be
highly sensitive to the stacking potential, mostly to its nonlinear parameters.
We find that the J-factor generally decreases by reducing the sequence length (
N ) and, more significantly, below N = 100 base pairs. However, even for very
small molecules, the J-factors remain sizeable in line with recent experimental
indications. Large bending angles between adjacent base pairs and anharmonic
stacking appear as the causes of the helix flexibility at short length scales.Comment: The Journal of Chemical Physics - May 2016 ; 9 page
Differential hydrophobicity drives self-assembly in Huntington's disease
Identifying the driving forces and the mechanism of association of
huntingtin-exon1, a close marker for the progress of Huntington's disease, is
an important prerequisite towards finding potential drug targets, and
ultimately a cure. We introduce here a modelling framework based on a key
analogy of the physico-chemical properties of the exon1 fragment to block
copolymers. We use a systematic mesoscale methodology, based on Dissipative
Particle Dynamics, which is capable of overcoming kinetic barriers, thus
capturing the dynamics of significantly larger systems over longer times than
considered before. Our results reveal that the relative hydrophobicity of the
poly-glutamine block as compared to the rest of the (proline-based) exon1
fragment, ignored to date, constitutes a major factor in the initiation of the
self-assembly process. We find that the assembly is governed by both the
concentration of exon1 and the length of the poly-glutamine stretch, with a low
length threshold for association even at the lowest volume fractions we
considered. Moreover, this self-association occurs irrespective of whether the
glutamine stretch is in random coil or hairpin configuration, leading to
spherical or cylindrical assemblies, respectively. We discuss the implications
of these results for reinterpretation of existing research within this context,
including that the routes towards aggregation of exon1 may be distinct to those
of the widely studied homopolymeric poly-glutamine peptides
DNA cyclization and looping in the wormlike limit: normal modes and the validity of the harmonic approximation
For much of the last three decades Monte Carlo-simulation methods have been
the standard approach for accurately calculating the cyclization probability,
, or J factor, for DNA models having sequence-dependent bends or
inhomogeneous bending flexibility. Within the last ten years, however,
approaches based on harmonic analysis of semi-flexible polymer models have been
introduced, which offer much greater computational efficiency than Monte Carlo
techniques. These methods consider the ensemble of molecular conformations in
terms of harmonic fluctuations about a well-defined elastic-energy minimum.
However, the harmonic approximation is only applicable for small systems,
because the accessible conformation space of larger systems is increasingly
dominated by anharmonic contributions. In the case of computed values of the J
factor, deviations of the harmonic approximation from the exact value of as
a function of DNA length have not been characterized. Using a recent,
numerically exact method that accounts for both anharmonic and harmonic
contributions to for wormlike chains of arbitrary size, we report here the
apparent error that results from neglecting anharmonic behavior. For wormlike
chains having contour lengths less than four times the persistence length the
error in arising from the harmonic approximation is generally small,
amounting to free energies less than the thermal energy, . For larger
systems, however, the deviations between harmonic and exact values increase
approximately linearly with size.Comment: 23 pages, 6 figures. Typos corrected. Manuscript improve
Knowledge-based energy functions for computational studies of proteins
This chapter discusses theoretical framework and methods for developing
knowledge-based potential functions essential for protein structure prediction,
protein-protein interaction, and protein sequence design. We discuss in some
details about the Miyazawa-Jernigan contact statistical potential,
distance-dependent statistical potentials, as well as geometric statistical
potentials. We also describe a geometric model for developing both linear and
non-linear potential functions by optimization. Applications of knowledge-based
potential functions in protein-decoy discrimination, in protein-protein
interactions, and in protein design are then described. Several issues of
knowledge-based potential functions are finally discussed.Comment: 57 pages, 6 figures. To be published in a book by Springe
Equation of state and critical behavior of polymer models: A quantitative comparison between Wertheim's thermodynamic perturbation theory and computer simulations
We present an application of Wertheim's Thermodynamic Perturbation Theory
(TPT1) to a simple coarse grained model made of flexibly bonded Lennard-Jones
monomers. We use both the Reference Hyper-Netted-Chain (RHNC) and Mean
Spherical approximation (MSA) integral equation theories to describe the
properties of the reference fluid. The equation of state, the density
dependence of the excess chemical potential, and the critical points of the
liquid--vapor transition are compared with simulation results and good
agreement is found. The RHNC version is somewhat more accurate, while the MSA
version has the advantage of being almost analytic. We analyze the scaling
behavior of the critical point of chain fluids according to TPT1 and find it to
reproduce the mean field exponents: The critical monomer density is predicted
to vanish as upon increasing the chain length while the critical
temperature is predicted to reach an asymptotic finite temperature that is
attained as . The predicted asymptotic finite critical temperature
obtained from the RHNC and MSA versions of TPT1 is found to be in good
agreement with the point of our polymer model as obtained from the
temperature dependence of the single chain conformations.Comment: to appear in J.Chem.Phy
Single-molecule pulling: phenomenology and interpretation
Single-molecule pulling techniques have emerged as versatile tools for
probing the noncovalent forces holding together the secondary and tertiary
structure of macromolecules. They also constitute a way to study at the
single-molecule level processes that are familiar from our macroscopic
thermodynamic experience. In this Chapter, we summarize the essential
phenomenology that is typically observed during single-molecule pulling,
provide a general statistical mechanical framework for the interpretation of
the equilibrium force spectroscopy and illustrate how to simulate
single-molecule pulling experiments using molecular dynamics.Comment: arXiv admin note: text overlap with arXiv:0908.220
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