703 research outputs found
A Multicanonical Molecular Dynamics Study on a Simple Bead-Spring Model for Protein Folding
We have performed a multicanonical molecular dynamics simulation on a simple
model protein.We have studied a model protein composed of charged, hydrophobic,
and neutral spherical bead monomers.Since the hydrophobic interaction is
considered to significantly affect protein folding, we particularly focus on
the competition between effects of the Coulomb interaction and the hydrophobic
interaction. We found that the transition which occurs upon decreasing the
temperature is markedly affected by the change in both parameters and forms of
the hydrophobic potential function, and the transition changes from first order
to second order, when the Coulomb interaction becomes weaker.Comment: 7 pages, 6 postscript figures, To appear in J.Phys.Soc.Jpn. Vol.70
No.
Highly Designable Protein Structures and Inter Monomer Interactions
By exact computer enumeration and combinatorial methods, we have calculated
the designability of proteins in a simple lattice H-P model for the protein
folding problem.
We show that if the strength of the non-additive part of the interaction
potential becomes larger than a critical value, the degree of designability of
structures will depend on the parameters of potential. We also show that the
existence of a unique ground state is highly sensitive to mutation in certain
sites.Comment: 14 pages, Latex file, 3 latex and 6 eps figures are include
Thermodynamics of aggregation of two proteins
We investigate aggregation mechanism of two proteins in a thermodynamically
unambiguous manner by considering the finite size effect of free energy
landscape of HP lattice protein model. Multi-Self-Overlap-Ensemble Monte Carlo
method is used for numerical calculations. We find that a dimer can be formed
spontaneously as a thermodynamically stable state when the system is small
enough. It implies the possibility that the aggregation of proteins in a cell
is triggered when they are confined in a small region by, for example, being
surrounded by other macromolecules.We also find that the dimer exhibits a
transition between unstable state and metastable state in the infinite system.Comment: jpsj2.cls, 7 pages, 14 figures; misconfigurations of Fig.Nos.
correcte
Sequence Dependence of Self-Interacting Random Chains
We study the thermodynamic behavior of the random chain model proposed by
Iori, Marinari and Parisi, and how this depends on the actual sequence of
interactions along the chain. The properties of randomly chosen sequences are
compared to those of designed ones, obtained through a simulated annealing
procedure in sequence space. We show that the transition to the folded phase
takes place at a smaller strength of the quenched disorder for designed
sequences. As a result, folding can be relatively fast for these sequences.Comment: 14 pages, uuencoded compressed postscript fil
Reply to Comment on "Criterion that Determines the Foldability of Proteins"
We point out that the correlation between folding times and in protein-like heteropolymer models where
and are the collapse and folding transition temperatures
was already established in 1993 before the other presumed equivalent criterion
(folding times correlating with alone) was suggested. We argue that the
folding times for these models show no useful correlation with the energy gap
even if restricted to the ensemble of compact structures as suggested by
Karplus and Shakhnovich (cond-mat/9606037).Comment: 6 pages, Latex, 2 Postscript figures. Plots explicitly showing the
lack of correlation between folding time and energy gap are adde
Deriving amino acid contact potentials from their frequencies of occurence in proteins: a lattice model study
The possibility of deriving the contact potentials between amino acids from
their frequencies of occurence in proteins is discussed in evolutionary terms.
This approach allows the use of traditional thermodynamics to describe such
frequencies and, consequently, to develop a strategy to include in the
calculations correlations due to the spatial proximity of the amino acids and
to their overall tendency of being conserved in proteins. Making use of a
lattice model to describe protein chains and defining a "true" potential, we
test these strategies by selecting a database of folding model sequences,
deriving the contact potentials from such sequences and comparing them with the
"true" potential. Taking into account correlations allows for a markedly better
prediction of the interaction potentials
Geometrically Reduced Number of Protein Ground State Candidates
Geometrical properties of protein ground states are studied using an
algebraic approach. It is shown that independent from inter-monomer
interactions, the collection of ground state candidates for any folded protein
is unexpectedly small: For the case of a two-parameter Hydrophobic-Polar
lattice model for -mers, the number of these candidates grows only as .
Moreover, the space of the interaction parameters of the model breaks up into
well-defined domains, each corresponding to one ground state candidate, which
are separated by sharp boundaries. In addition, by exact enumeration, we show
there are some sequences which have one absolute unique native state. These
absolute ground states have perfect stability against change of inter-monomer
interaction potential.Comment: 9 page, 4 ps figures are include
Entropic Barriers, Frustration and Order: Basic Ingredients in Protein Folding
We solve a model that takes into account entropic barriers, frustration, and
the organization of a protein-like molecule. For a chain of size , there is
an effective folding transition to an ordered structure. Without frustration,
this state is reached in a time that scales as , with
. This scaling is limited by the amount of frustration which
leads to the dynamical selectivity of proteins: foldable proteins are limited
to monomers; and they are stable in {\it one} range of temperatures,
independent of size and structure. These predictions explain generic properties
of {\it in vivo} proteins.Comment: 4 pages, 4 Figures appended as postscript fil
Simple models of protein folding and of non--conventional drug design
While all the information required for the folding of a protein is contained
in its amino acid sequence, one has not yet learned how to extract this
information to predict the three--dimensional, biologically active, native
conformation of a protein whose sequence is known. Using insight obtained from
simple model simulations of the folding of proteins, in particular of the fact
that this phenomenon is essentially controlled by conserved (native) contacts
among (few) strongly interacting ("hot"), as a rule hydrophobic, amino acids,
which also stabilize local elementary structures (LES, hidden, incipient
secondary structures like --helices and --sheets) formed early
in the folding process and leading to the postcritical folding nucleus (i.e.,
the minimum set of native contacts which bring the system pass beyond the
highest free--energy barrier found in the whole folding process) it is possible
to work out a succesful strategy for reading the native structure of designed
proteins from the knowledge of only their amino acid sequence and of the
contact energies among the amino acids. Because LES have undergone millions of
years of evolution to selectively dock to their complementary structures, small
peptides made out of the same amino acids as the LES are expected to
selectively attach to the newly expressed (unfolded) protein and inhibit its
folding, or to the native (fluctuating) native conformation and denaturate it.
These peptides, or their mimetic molecules, can thus be used as effective
non--conventional drugs to those already existing (and directed at neutralizing
the active site of enzymes), displaying the advantage of not suffering from the
uprise of resistance
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