An easy-to-use, versatile and freely available graphic web server, FoldIndex is described: it predicts if a given protein sequence is intrinsically unfolded implementing the algorithm of Uversky and co-workers, which is based on the average residue hydrophobicity and net charge of the sequence. FoldIndex has an error rate comparable to that of more sophisticated fold prediction methods. Sliding windows permit identification of large regions within a protein that possess folding propensities different from those of the whole protein.

This paper describes a new concept in the way information can be protected at the molecular scale. By harnessing the principles of molecular Boolean logic, we have designed a molecular device that mimics the operation of an electronic keypad lock, e.g., a common security circuit used for numerous applications, in which access to an object or data is to be restricted to a limited number of persons. What distinguishes this lock from a simple molecular logic gate is the fact that its output signals are dependent not only on the proper combination of the inputs but also on the correct order by which these inputs are introduced. In other words, one needs to know the exact passwords that open this lock. The different password entries are coded by a combination of two chemical and one optical input signals, which can activate, separately, blue or green fluorescence output channels from pyrene or fluorescein fluorophores. The information in each channel is a single-bit light output signal that can be used to authorize a user, to verify authentication of a product, or to initiate a higher process. This development not only opens the way for a new class of molecular decision-making devices but also adds a new dimension of protection to existing defense technologies, such as cryptography and steganography, previously achieved with molecules.

An Internet server at http://bip.weizmann.ac.il/dipol calculates the net charge, dipole moment and mean radius of any 3D protein structure or its constituent peptide chains, and displays the dipole vector superimposed on a ribbon backbone of the protein. The server can also display the angle between the dipole and a selected list of amino acid residues in the protein. When the net charges and dipole moments of ∼12 000 non-homologous PDB biological units (PISCES set), and their unique chains of length 50 residues or longer, were examined, the great majority of both charges and dipoles fell into a very narrow range of values, with long extended tails containing a few extreme outliers. In general, there is no obvious relation between a protein's charge or dipole moment and its structure or function, so that its electrostatic properties are highly specific to the particular protein, except that the majority of chains with very large positive charges or dipoles bind to ribosomes or interact with nucleic acids.

Availability of complete genome sequences allows in-depth comparison of single-residue and oligopeptide compositions of the corresponding proteomes. We have used principal component analysis (PCA) to study the landscape of compositional motifs across more than 70 genera from all three superkingdoms. Unexpectedly, the first two principal components clearly differentiate archaea, eubacteria, and eukaryota from each other. In particular, we contrast compositional patterns typical of the three superkingdoms and characterize differences between species and phyla, as well as among patterns shared by all compositional proteomic signatures. These species-specific patterns may even extend to subsets of the entire proteome, such as proteins pertaining to individual yeast chromosomes. We identify factors that affect compositional signatures, such as living habitat, and detect strong eukaryotic preference for homopeptides and palindromic tripeptides. We further detect oligopeptides that are either universally over- or underabundant across the whole proteomic landscape, as well as oligopeptides whose over- or underabundance is phylum- or species-specific. Finally, we report that species composition signatures preserve evolutionary memory, providing a new method to compare phylogenetic relationships among species that avoids problems of sequence alignment and ortholog detection.

Empirical force field studies of poly(alkyl isocyanates) are presented. A barrier of 12.5 kcal/ mol for cis-trans isomerization of the polymer-backbone's conjugated partial double bonds makes the calculated energy of helix sense reversal agree best with corresponding experimental results. The alternating cis and trans torsion angles are found to be distorted, to about 170°and -55°for right-handed helices, by strong repulsions between the -carbon of each alkyl side chain and the neighboring backbone atoms of four consecutive monomer units. Polyisocyanates are predicted to possess a soft collective internal motion, in which rotation per monomer around the polymer's helix axis varies widely, accompanied by large variations of the backbone's torsional angles, at low energy cost. When the ß carbon of a normal alkyl side chain acquires an absolute configuration (R) by methyl substitution, the left-handed helical conformation is predicted to be more stable than the right-handed one by about 0.5 kcal/mol per monomer unit. Reversal of the helical sense involves conformational change of several consecutive monomers, and the angle between the helices of opposite senses is about 130°.

DFT/B3LYP calculations were carried out on complexes formed by NH 4 + with aromatics, viz. benzene, phenol, pyrrole, imidazole, pyridine, indole, furane, and thiophene, to characterize the forces involved in such interactions and to gain further insight into the nature and diversity of cation-aromatic interactions. Such calculations may provide valuable information for understanding molecular recognition in biological systems and for force-field development. B3LYP/6-31G** optimization on 35 initial structures resulted in 11 different finally optimized geometries, which could be divided into three types: NH 4 + -π complexes, protonated heterocyclic-NH 3 hydrogen bond complexes, and heterocyclic-NH 4 + hydrogen bond complexes. For NH 4 + -π complexes, NH 4 + always tilts toward the carbon-carbon bond rather than toward the heteroatom or the carbonheteroatom bond. The calculated CHelpG charges suggest that the charge distribution of a free heterocyclic may be used to predict the geometry of its complex. Charge population and electrostatic interaction estimations show that the NH 4 + -π interaction has the largest nonelectrostatic interaction fraction (∼47%) of the total binding energy, while the NH 4 + -aromatic hydrogen bond interaction has the largest electrostatic fraction (∼90%). A good correlation between binding energy and electrostatic interaction in the NH 4 + -π complexes is found, which shows that nonelectrostatic interaction is important for cation-π binding. The results calculated with basis sets from 6-31G to 6-311++G(2df, 2dp) show that ∆E corr and ∆H corr do not require a basis-set superposition error (BSSE) correction, in view of experimental error, if a larger basis set is used in the calculation. The calculated ∆H corr values for the NH 4 + -C 6 H 6 complex with different basis sets suggest that the experimental ∆H may be overestimated.

We describe the design and function of a molecular logic system, by which a combinatorial recognition of the input signals is utilized to efficiently process chemically encoded information. Each chemical input can target simultaneously multiple domains on the same molecular platform, resulting in a unique combination of chemical states, each with its characteristic fluorescence output. Simple alteration of the input reagents changes the emitted logic pattern and enables it to perform different algebraic operations between two bits, solely in the fluorescence mode. This system exhibits parallelism in both its chemical inputs and light outputs.

To consider whether existing molecular force fields can adequately reproduce cation-π interactions without adding special interaction terms, theoretical calculations with geometry optimization were performed on three configurations of tetramethylammonium (TMA) interacting via one, two, or three N-methyl groups with a benzene ring, by use of density-functional theory (DFT) methods B3LYP/6-31G* and B3LYP/6-311G**, ab initio method MP2/6-31G*, and molecular mechanic methods EFF, Tinker's Amber and MM3. Only the first configuration was found to be stable from the DFT and MP2 results, and its geometry was found to be highly flexible. ESP CHELPG charges estimated from the DFT and MP2 calculations were used to modify the atomic charges of the force fields employed in the molecular mechanics calculations to improve agreement with the BSSE-corrected binding energies deduced from the DFT and MP2 results. After this modification, the molecular mechanics results were found to be in good agreement with those obtained by DFT and MP2, without a requirement to add any additional terms to the force fields. This was confirmed by comparing the energy profiles of the complex as benzene was moved away from TMA in 0.2 Å intervals. Hence it is possible to use existing force fields to represent cation-π interactions by a simple adjustment of certain partial atomic charge parameters. In this context, we discuss the high flexibility of the cation-π interactions in the framework of molecular recognition in biological systems.