Bioinformatics

Effective function annotation through catalytic residue conservation

Although comparative sequence analysis can be useful for determining function of unknown proteins, the reliability of prediction drops dramatically as the extent of sequence identity decreases. George et al. show that the inclusion of strict active site–based analysis, using data from the Catalytic Site Atlas, greatly improves the accuracy of functional analysis.

George, R.A. et al. Proc. Natl. Acad. Sci. USA; published online 21 July, 2005.

Spectroscopy

Multidimensional NMR spectroscopy for protein characterization and assignment inside cells

Reardon and Spicer have taken advantage of new advances in nuclear magnetic resonance (NMR) to develop a heteronuclear, three-dimensional spectroscopy strategy capable of providing full backbone assignments for any protein in-cell. As proof of concept, the authors successfully assign the backbone for the Escherichia coli protein GB-1 with three rapid NMR experiments.

Reardon, P.N. & Spicer, L.D. J. Am. Chem. Soc. 127, 10848–10849 (2005).

Molecular libraries

Functional dissection of sRNA translational regulators by nonhomologous random recombination and in vivo selection

Nonhomologous random recombination has been previously demonstrated as a useful strategy for the directed evolution of DNA aptamers and functionally modified enzymes. Now, Liu et al. use this technique to identify the key structural determinants that allow a pair of small, nontranslated RNAs (sRNAs) to regulate translation of a stress response gene in Escherichia coli.

Liu, J.M. et al. Chem. Biol. 12, 757–767 (2005).

Gene delivery

Organically modified silica nanoparticles: a nonviral vector for in vivo gene delivery and expression in the brain

Finding safe and effective methods for the delivery of therapeutic genes to the brain has proven to be a challenging task. Bharali et al. present a new strategy for the delivery of DNA via organically modified silica particles, permitting efficient transfection of neurons after ventricular injection, without the inherent risks of retroviral or other delivery systems.

Bharali, D.J. et al. Proc. Natl. Acad. Sci. USA 102, 11539–11544 (2005).

Cheminformatics

High-throughput assays for promiscuous inhibitors

Several different mechanisms have been suggested to explain why certain chemical compounds act as reduced-specificity, or promiscuous, inhibitors. Feng et al. suggest that aggregation may be a major cause for promiscuity and present two rapid assays developed specifically to assess the extent of aggregation by compounds contained in chemical libraries.

Feng, B.Y. et al. Nat. Chem. Biol. 1, 146–148 (2005).