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

Statistical Properties of Contact Maps

A contact map is a simple representation of the structure of proteins and other chain-like macromolecules. This representation is quite amenable to numerical studies of folding. We show that the number of contact maps corresponding to the possible configurations of a polypeptide chain of N amino acids, represented by (N-1)-step self avoiding walks on a lattice, grows exponentially with N for all dimensions D>1. We carry out exact enumerations in D=2 on the square and triangular lattices for walks of up to 20 steps and investigate various statistical properties of contact maps corresponding to such walks. We also study the exact statistics of contact maps generated by walks on a ladder.Comment: Latex file, 15 pages, 12 eps figures. To appear on Phys. Rev.

Translationally optimal codons associate with aggregation-prone sites in proteins

We analyze the relationship between codon usage bias and residue aggregation propensity in the genomes of four model organisms, Escherichia coli, yeast, fly, and mouse, as well as the archaeon Halobacterium species NRC-1. Using the Mantel-Haenszel procedure, we find that translationally optimal codons associate with aggregation-prone residues. Our results are qualitatively and quantitatively similar to those of an earlier study where we found an association between translationally optimal codons and buried residues. We also combine the aggregation-propensity data with solvent-accessibility data. Although the resulting data set is small, and hence statistical power low, results indicate that the association between optimal codons and aggregation-prone residues exists both at buried and at exposed sites. By comparing codon usage at different combinations of sites (exposed, aggregation-prone sites versus buried, non-aggregation-prone sites; buried, aggregation-prone sites versus exposed, non-aggregation-prone sites), we find that aggregation propensity and solvent accessibility seem to have independent effects of (on average) comparable magnitude on codon usage. Finally, in fly, we assess whether optimal codons associate with sites at which amino acid substitutions lead to an increase in aggregation propensity, and find only a very weak effect. These results suggest that optimal codons may be required to reduce the frequency of translation errors at aggregation-prone sites that coincide with certain functional sites, such as protein-protein interfaces. Alternatively, optimal codons may be required for rapid translation of aggregation-prone regions. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

On the form of growing strings

Patterns and forms adopted by Nature, such as the shape of living cells, the geometry of shells and the branched structure of plants, are often the result of simple dynamical paradigms. Here we show that a growing self-interacting string attached to a tracking origin, modeled to resemble nascent polypeptides in vivo, develops helical structures which are more pronounced at the growing end. We also show that the dynamic growth ensemble shares several features of an equilibrium ensemble in which the growing end of the polymer is under an effective stretching force. A statistical analysis of native states of proteins shows that the signature of this non-equilibrium phenomenon has been fixed by evolution at the C-terminus, the growing end of a nascent protein. These findings suggest that a generic non-equilibrium growth process might have provided an additional evolutionary advantage for nascent proteins by favoring the preferential selection of helical structures.Comment: 4 pages, 3 figures. Accepted for publication in Phys. Rev. Let

Identification of pesticide-degrading Pseudomonas strains as poly-B-hydroxybutyrate producers.

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