1,057 research outputs found
Statistical properties of contact vectors
We study the statistical properties of contact vectors, a construct to
characterize a protein's structure. The contact vector of an N-residue protein
is a list of N integers n_i, representing the number of residues in contact
with residue i. We study analytically (at mean-field level) and numerically the
amount of structural information contained in a contact vector. Analytical
calculations reveal that a large variance in the contact numbers reduces the
degeneracy of the mapping between contact vectors and structures. Exact
enumeration for lengths up to N=16 on the three dimensional cubic lattice
indicates that the growth rate of number of contact vectors as a function of N
is only 3% less than that for contact maps. In particular, for compact
structures we present numerical evidence that, practically, each contact vector
corresponds to only a handful of structures. We discuss how this information
can be used for better structure prediction.Comment: 20 pages, 6 figure
Reconstruction of protein structures from a vectorial representation
We show that the contact map of the native structure of globular proteins can
be reconstructed starting from the sole knowledge of the contact map's
principal eigenvector, and present an exact algorithm for this purpose. Our
algorithm yields a unique contact map for all 221 globular structures of
PDBselect25 of length . We also show that the reconstructed contact
maps allow in turn for the accurate reconstruction of the three-dimensional
structure. These results indicate that the reduced vectorial representation
provided by the principal eigenvector of the contact map is equivalent to the
protein structure itself. This representation is expected to provide a useful
tool in bioinformatics algorithms for protein structure comparison and
alignment, as well as a promising intermediate step towards protein structure
prediction.Comment: 4 pages, 1 figur
Protein folding using contact maps
We present the development of the idea to use dynamics in the space of
contact maps as a computational approach to the protein folding problem. We
first introduce two important technical ingredients, the reconstruction of a
three dimensional conformation from a contact map and the Monte Carlo dynamics
in contact map space. We then discuss two approximations to the free energy of
the contact maps and a method to derive energy parameters based on perceptron
learning. Finally we present results, first for predictions based on threading
and then for energy minimization of crambin and of a set of 6 immunoglobulins.
The main result is that we proved that the two simple approximations we studied
for the free energy are not suitable for protein folding. Perspectives are
discussed in the last section.Comment: 29 pages, 10 figure
A method of incorporating rate constants as kinetic constraints in molecular dynamics simulations
Self-Templated Nucleation in Peptide and Protein aggregation
Peptides and proteins exhibit a common tendency to assemble into highly
ordered fibrillar aggregates, whose formation proceeds in a
nucleation-dependent manner that is often preceded by the formation of
disordered oligomeric assemblies. This process has received much attention
because disordered oligomeric aggregates have been associated with
neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Here
we describe a self-templated nucleation mechanism that determines the
transition between the initial condensation of polypeptide chains into
disordered assemblies and their reordering into fibrillar structures. The
results that we present show that at the molecular level this transition is due
to the ability of polypeptide chains to reorder within oligomers into fibrillar
assemblies whose surfaces act as templates that stabilise the disordered
assemblies.Comment: 4 pages, 3 figure
The Origin of the Designability of Protein Structures
We examined what determines the designability of 2-letter codes (H and P)
lattice proteins from three points of view. First, whether the native structure
is searched within all possible structures or within maximally compact
structures. Second, whether the structure of the used lattice is bipartite or
not. Third, the effect of the length of the chain, namely, the number of
monomers on the chain. We found that the bipartiteness of the lattice structure
is not a main factor which determines the designability. Our results suggest
that highly designable structures will be found when the length of the chain is
sufficiently long to make the hydrophobic core consisting of enough number of
monomers.Comment: 17 pages, 2 figure
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A Cell- and Tissue-Specific Weakness of the Protein Homeostasis System Underlies Brain Vulnerability to Protein Aggregation.
The phenomenon of protein misfolding and aggregation is associated with a wide range of neurodegenerative conditions that cause progressive loss of function in specific regions of the human brain. To understand the causes of the selective cell and tissue vulnerability to the formation of these deposits, we analyzed the ability of different cell and tissue types to respond, in the absence of disease, to the presence of high levels of aggregation-prone proteins. By performing a transcriptional analysis, we found that the protein homeostasis system that regulates protein aggregation is weaker in neurons than in other cell types and in brain tissues than in other body tissues. These results suggest that the intrinsic level of regulation of protein aggregation in the healthy state is correlated with the selective vulnerability of cells and tissues to protein misfolding diseases
Prediction of Local Structural Stabilities of Proteins from Their Amino Acid Sequences
Hydrogen exchange experiments provide detailed information about the local stability and the solvent accessibility of different regions of the structures of folded proteins, protein complexes, and amyloid fibrils. We introduce an approach to predict protection factors from hydrogen exchange in proteins based on the knowledge of their amino acid sequences without the inclusion of any additional structural information. These results suggest that the propensity of different regions of the structures of globular proteins to undergo local unfolding events can be predicted from their amino acid sequences with an accuracy of 80% or better. © 2007 Elsevier Ltd. All rights reserved
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