321 research outputs found
Folding and Design in Coarse-Grained Protein Models
Recent advances in coarse-grained lattice and off-lattice protein models are
reviewed. The sequence dependence of thermodynamical folding properties are
investigated and evidence for non-randomness of the binary sequences of good
folders are discussed. Similar patterns for non-randomness are found for real
proteins. Dynamical parameter MC methods, such as the tempering and
multisequence algorithms, are essential in order to obtain these results. Also,
a new MC method for design, the inverse of folding, is presented. Here, one
maximizes conditional probabilities rather than minimizing energies. By
construction, this method ensures that the designed sequences represent good
folders thermodynamically.Comment: LATTICE 99 (Spin Models), 3 pages, 1 figure, espcrc2.st
Hybrid Monte Carlo simulation of polymer chains
We develop the hybrid Monte Carlo method for simulations of single
off-lattice polymer chains. We discuss implementation and choice of simulation
parameters in some detail. The performance of the algorithm is tested on models
for homopolymers with short- or long-range self-repulsion, using chains with
monomers. Without excessive fine tuning, we find that the
computational cost grows as with . In
addition, we report results for the scaling of the end-to-end distance,
.Comment: 13 pages, single postscript file, uuencoded form, Lund Preprint LU-TP
93-2
Thermodynamics of amyloid formation and the role of intersheet interactions
The self-assembly of proteins into -sheet-rich amyloid fibrils has
been observed to occur with sigmoidal kinetics, indicating that the system
initially is trapped in a metastable state. Here, we use a minimal
lattice-based model to explore the thermodynamic forces driving amyloid
formation in a finite canonical () system. By means of
generalized-ensemble Monte Carlo techniques and a semi-analytical method, the
thermodynamic properties of this model are investigated for different sets of
intersheet interaction parameters. When the interactions support lateral growth
into multi-layered fibrillar structures, an evaporation/condensation transition
is observed, between a supersaturated solution state and a thermodynamically
distinct state where small and large fibril-like species exist in equilibrium.
Intermediate-size aggregates are statistically suppressed. These properties do
not hold if aggregate growth is one-dimensional.Comment: 22 page
Design of Sequences with Good Folding Properties in Coarse-Grained Protein Models
Background: Designing amino acid sequences that are stable in a given target
structure amounts to maximizing a conditional probability. A straightforward
approach to accomplish this is a nested Monte Carlo where the conformation
space is explored over and over again for different fixed sequences, which
requires excessive computational demand. Several approximate attempts to remedy
this situation, based on energy minimization for fixed structure or high-
expansions, have been proposed. These methods are fast but often not accurate
since folding occurs at low .
Results: We develop a multisequence Monte Carlo procedure, where both
sequence and conformation space are simultaneously probed with efficient
prescriptions for pruning sequence space. The method is explored on
hydrophobic/polar models. We first discuss short lattice chains, in order to
compare with exact data and with other methods. The method is then successfully
applied to lattice chains with up to 50 monomers, and to off-lattice 20-mers.
Conclusions: The multisequence Monte Carlo method offers a new approach to
sequence design in coarse-grained models. It is much more efficient than
previous Monte Carlo methods, and is, as it stands, applicable to a fairly wide
range of two-letter models.Comment: 23 pages, 7 figure
Local Interactions and Protein Folding: A Model Study on the Square and Triangular Lattices
We study a simple heteropolymer model containing sequence-independent local
interactions on both square and triangular lattices. Sticking to a two-letter
code, we investigate the model for varying strength of the local
interactions; corresponds to the well-known HP model [K.F. Lau and
K.A. Dill, Macromolecules 22, 3986 (1989)]. By exhaustive enumerations for
short chains, we obtain all structures which act as a unique and pronounced
energy minimum for at least one sequence. We find that the number of such
designable structures depends strongly on . Also, we find that the
number of designable structures can differ widely for the two lattices at a
given . This is the case, for example, at , which implies
that the HP model exhibits different behavior on the two lattices. Our findings
clearly show that sequence-independent local properties of the chains can play
an important role in the formation of unique minimum energy structures.Comment: 10 pages LaTeX, 3 Postscript figures. Figure and references adde
Enumerating Designing Sequences in the HP Model
The hydrophobic/polar HP model on the square lattice has been widely used to
investigate basics of protein folding. In the cases where all designing
sequences (sequences with unique ground states) were enumerated without
restrictions on the number of contacts, the upper limit on the chain length N
has been 18-20 because of the rapid exponential growth of the numbers of
conformations and sequences. We show how a few optimizations push this limit by
about 5 units. Based on these calculations, we study the statistical
distribution of hydrophobicity along designing sequences. We find that the
average number of hydrophobic and polar clumps along the chains is larger for
designing sequences than for random ones, which is in agreement with earlier
findings for N up to 18 and with results for real enzymes. We also show that
this deviation from randomness disappears if the calculations are restricted to
maximally compact structures.Comment: 18 pages, 4 figure
Binary Assignments of Amino Acids from Pattern Conservation
We develop a simple optimization procedure for assigning binary values to the
amino acids. The binary values are determined by a maximization of the degree
of pattern conservation in groups of closely related protein sequences. The
maximization is carried out at fixed composition. For compositions
approximately corresponding to an equipartition of the residues, the optimal
encoding is found to be strongly correlated with hydrophobicity. The stability
of the procedure is demonstrated. Our calculations are based upon sequences in
the SWISS-PROT database.Comment: 9 pages, 4 Postscript figures. References and figure adde
Coupled folding-binding versus docking: A lattice model study
Using a simple hydrophobic/polar protein model, we perform a Monte Carlo
study of the thermodynamics and kinetics of binding to a target structure for
two closely related sequences, one of which has a unique folded state while the
other is unstructured. We obtain significant differences in their binding
behavior. The stable sequence has rigid docking as its preferred binding mode,
while the unstructured chain tends to first attach to the target and then fold.
The free-energy profiles associated with these two binding modes are compared.Comment: 17 pages, 7 figures (to appear in J. Chem. Phys.
Folding thermodynamics of three beta-sheet peptides: A model study
We study the folding thermodynamics of a beta-hairpin and two three-stranded
beta-sheet peptides using a simplified sequence-based all-atom model, in which
folding is driven mainly by backbone hydrogen bonding and effective hydrophobic
attraction. The native populations obtained for these three sequences are in
good agreement with experimental data. We also show that the apparent native
population depends on which observable is studied; the hydrophobicity energy
and the number of native hydrogen bonds give different results. The magnitude
of this dependence matches well with the results obtained in two different
experiments on the beta-hairpin.Comment: 17 pages, 7 figures, to appear in Protein
Studies of an Off-Lattice Model for Protein Folding: Sequence Dependence and Improved Sampling at Finite Temperature
We study the thermodynamic behavior of a simple off-lattice model for protein
folding. The model is two-dimensional and has two different ``amino acids''.
Using numerical simulations of all chains containing eight or ten monomers, we
examine the sequence dependence at a fixed temperature. It is shown that only a
few of the chains exist in unique folded state at this temperature, and the
energy level spectra of chains with different types of behavior are compared.
Furthermore, we use this model as a testbed for two improved Monte Carlo
algorithms. Both algorithms are based on letting some parameter of the model
become a dynamical variable; one of the algorithms uses a fluctuating
temperature and the other a fluctuating monomer sequence. We find that by these
algorithms one gains large factors in efficiency in comparison with
conventional methods.Comment: 17 pages, 9 Postscript figures. Combined with chem-ph/950500
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