38 research outputs found
Chirality and Protein Folding
There are several simple criteria of folding to a native state in model
proteins. One of them involves crossing of a threshold value of the RMSD
distance away from the native state. Another checks whether all native contacts
are established, i.e. whether the interacting amino acids come closer than some
characteristic distance. We use Go-like models of proteins and show that such
simple criteria may prompt one to declare folding even though fragments of the
resulting conformations have a wrong sense of chirality. We propose that a
better condition of folding should augment the simple criteria with the
requirement that most of the local values of the chirality should be nearly
native. The kinetic discrepancy between the simple and compound criteria can be
substantially reduced in the Go-like models by providing the Hamiltonian with a
term which favors native values of the local chirality. We study the effects of
this term as a function of its amplitude and compare it to other models such as
with the side groups and with the angle-dependent potentials.Comment: To be published in a special issue of J. Phys.: Cond. Mat. (Bedlewo
Workshop
Delineation of the Native Basin in Continuum Models of Proteins
We propose two approaches for determining the native basins in off-lattice
models of proteins. The first of them is based on exploring the saddle points
on selected trajectories emerging from the native state. In the second
approach, the basin size can be determined by monitoring random distortions in
the shape of the protein around the native state. Both techniques yield the
similar results. As a byproduct, a simple method to determine the folding
temperature is obtained.Comment: REVTeX, 6 pages, 5 EPS figure
Thermodynamic stability of folded proteins against mutations
By balancing the average energy gap with its typical change due to mutations
for protein-like heteropolymers with M residues, we show that native states are
unstable to mutations on a scale M* ~ (lambda/sigma_mu)^(1/zeta_s), where
lambda is the dispersion in the interaction free energies and sigma_mu their
typical change. Theoretical bounds and numerical estimates (based on complete
enumeration on four lattices) of the instability exponent zeta_s are given. Our
analysis suggests that a limiting size of single-domain proteins should exist,
and leads to the prediction that small proteins are insensitive to random
mutations.Comment: 5 pages, 3 figures, to be published in Physical Review Letter
Viscosity Dependence of the Folding Rates of Proteins
The viscosity dependence of the folding rates for four sequences (the native
state of three sequences is a beta-sheet, while the fourth forms an
alpha-helix) is calculated for off-lattice models of proteins. Assuming that
the dynamics is given by the Langevin equation we show that the folding rates
increase linearly at low viscosities \eta, decrease as 1/\eta at large \eta and
have a maximum at intermediate values. The Kramers theory of barrier crossing
provides a quantitative fit of the numerical results. By mapping the simulation
results to real proteins we estimate that for optimized sequences the time
scale for forming a four turn \alpha-helix topology is about 500 nanoseconds,
whereas the time scale for forming a beta-sheet topology is about 10
microseconds.Comment: 14 pages, Latex, 3 figures. One figure is also available at
http://www.glue.umd.edu/~klimov/seq_I_H.html, to be published in Physical
Review Letter
Folding in two-dimenensional off-lattice models of proteins
Model off-lattice sequences in two dimensions are constructed so that their
native states are close to an on-lattice target. The Hamiltonian involves the
Lennard-Jones and harmonic interactions. The native states of these sequences
are determined with a high degree of certainty through Monte Carlo processes.
The sequences are characterized thermodynamically and kinetically. It is shown
that the rank-ordering-based scheme of the assignment of contact energies
typically fails in off-lattice models even though it generates high stability
of on-lattice sequences. Similar to the on-lattice case, Go-like modeling, in
which the interaction potentials are restricted to the native contacts in a
target shape, gives rise to good folding properties. Involving other contacts
deteriorates these properties.Comment: REVTeX, 9 pages, 8 EPS figure
Folding, Design and Determination of Interaction Potentials Using Off-Lattice Dynamics of Model Heteropolymers
We present the results of a self-consistent, unified molecular dynamics study
of simple model heteropolymers in the continuum with emphasis on folding,
sequence design and the determination of the interaction parameters of the
effective potential between the amino acids from the knowledge of the native
states of the designed sequences.Comment: 8 pages, 3 Postscript figures, uses RevTeX. Submitted to Physical
Review Letter
Influence of Hydrodynamic Interactions on Mechanical Unfolding of Proteins
We incorporate hydrodynamic interactions in a structure-based model of
ubiquitin and demonstrate that the hydrodynamic coupling may reduce the peak
force when stretching the protein at constant speed, especially at larger
speeds. Hydrodynamic interactions are also shown to facilitate unfolding at
constant force and inhibit stretching by fluid flows.Comment: to be published in Journal of Physics: Condensed Matte
Modeling study on the validity of a possibly simplified representation of proteins
The folding characteristics of sequences reduced with a possibly simplified
representation of five types of residues are shown to be similar to their
original ones with the natural set of residues (20 types or 20 letters). The
reduced sequences have a good foldability and fold to the same native structure
of their optimized original ones. A large ground state gap for the native
structure shows the thermodynamic stability of the reduced sequences. The
general validity of such a five-letter reduction is further studied via the
correlation between the reduced sequences and the original ones. As a
comparison, a reduction with two letters is found not to reproduce the native
structure of the original sequences due to its homopolymeric features.Comment: 6 pages with 4 figure
Capturing the essence of folding and functions of biomolecules using Coarse-Grained Models
The distances over which biological molecules and their complexes can
function range from a few nanometres, in the case of folded structures, to
millimetres, for example during chromosome organization. Describing phenomena
that cover such diverse length, and also time scales, requires models that
capture the underlying physics for the particular length scale of interest.
Theoretical ideas, in particular, concepts from polymer physics, have guided
the development of coarse-grained models to study folding of DNA, RNA, and
proteins. More recently, such models and their variants have been applied to
the functions of biological nanomachines. Simulations using coarse-grained
models are now poised to address a wide range of problems in biology.Comment: 37 pages, 8 figure