Abstract not found

. A reduction from "Ground State of Spin Glass" in statistical mechanics to a minimumenergy model of protein folding is made, which shows that the latter is NP-complete (high complexity) . The reduction approximates true folding of a protein. The method also enables to show that even if the backbone of the protein is fixed, the folding of the side-chains is NP-complete. In a separate second part, the possibility of synthesizing proteins to solve arbitrary instances of the spin glass problem is speculated upon. 1. Introduction The motivation for this work is the speculation of exploiting nature's capability of protein folding to solve computationally intractable problems. One way of investigating this idea is to encode known NP-complete problems in terms of protein folding. The main content of this paper is to do this for the spin glass problem. We construct a protein that achieves the encoding, i.e., the folded protein provides a solution to spin glass. More precisely, albeit incident...

To investigate how the properties of individual amino acids result in proteins with particular structures and functions, we have examined the correlations between previously derived structure-dependent mutation rates and changes in various physicalchemical properties of the amino acids such as volume, charge, a-helical and b-sheet propensity, and hydrophobicity. In most cases we found the DG of transfer from octanol to water to be the best model for evolutionary constraints, in contrast to the much weaker correlation with the DG of transfer from cyclohexane to water, a property found to be highly correlated to changes in stability in sitedirected mutagenesis studies. This suggests that natural evolution may follow different rules than those suggested by results obtained in the laboratory. A high degree of conservation of a surface residue's relative hydrophobicity was also observed, a fact that cannot be explained by constraints on protein stability but that may reflect the consequence...

Only a minute fraction of all possible protein sequences can exist in the genomes of all life forms. To explore whether physicochemical constraints or a lack of need causes the paucity of different protein folds, we set out to construct protein libraries without any restriction of topology. We generated different libraries (all #-helix, all #-strand, and #-helix plus #-strand) with an average length of 100 amino acid residues, composed of designed secondary structure modules (#-helix, #-strand, and #-turn) in various proportions, based primarily on the patterning of polar and nonpolar residues. We wished to explore that part of sequence space that is rich in secondary structure. The analysis of randomly chosen clones from each of the libraries showed that, despite the low sequence homology to known protein sequences, a substantial proportion of the library members containing #-helix modules were indeed helical, possess a defined oligomerization state, and showed cooperative chemical unfolding behavior. On the other hand, proteins composed of mainly #-strand modules tended to form amyloid-like fibrils and were among the least soluble proteins ever reported. We found that a large fraction of members in non-#-strand--containing protein libraries that are distant from natural proteins in sequence space possess unexpectedly favorable properties. These results reinforce the efficacy of applying binary patterning to design proteins with native-like properties despite lack of restriction in topology. Because of the intrinsic tendency of #-strand modules to aggregate, their presence requires precise topologic arrangement to prevent fibril formation.

Abstract not found

: A minimal off-lattice model for ff-helical proteins is presented. It is based on hydrophobicity forces and sequence independent local interactions. The latter are chosen so as to favor the formation of ff-helical structure. They model chirality and ff-helical hydrogen bonding. The global structures resulting from the competition between these forces are studied by means of an efficient Monte Carlo method. The model is tested on two sequences of length N=21 and 33 which are intended to form 2- and 3-helix bundles, respectively. The local structure of our model proteins is compared to that of real ff-helical proteins, and is found to be very similar. The two sequences display the desired numbers of helices in the folded phase. Only a few different relative orientations of the helices are thermodynamically allowed. Our ability to investigate the thermodynamics relies heavily upon the efficiency of the used algorithm, simulated tempering; in this Monte Carlo approach, the temperature be...

Research article Metal ion-dependent, reversible, protein filament formation by designed beta-roll polypeptides