Nature Chemical Biology 5, 773 (2009). doi:10.1038/nchembio.258

Understanding how proteins function in isolation and in their native context requires a merging of molecular-level techniques that explore the interplay of protein structure and dynamics.

Nature Chemical Biology 5, 774 (2009). doi:10.1038/nchembio.241

Authors: Lila M Gierasch & Anne Gershenson

In their native environments, proteins perform their biological roles in highly concentrated viscous solutions and in complex networks with numerous partners. Yet for many years, the normal practice has been to purify a protein of interest in order to characterize its structural and functional properties. In this Commentary, we discuss how protein scientists are now tackling the theoretical and methodological challenges of studying proteins in their physiological context.

Nature Chemical Biology 5, 778 (2009). doi:10.1038/nchembio.233

Authors: Peter Tsvetkov, Nina Reuven & Yosef Shaul

Intrinsically disordered proteins (IDPs) are subject to ubiquitin-independent degradation, a default and passive process. We describe here a model wherein a group of 'nanny' proteins function to protect newly synthesized IDPs from degradation by default, thereby insuring their maturation into important regulatory molecules.

Nature Chemical Biology 5, 782 (2009). doi:10.1038/nchembio.245

Authors: Darren W Begley & Gabriele Varani

Few antimicrobial drugs function by directly targeting RNA. A small molecule that binds the hepatitis C viral genome by 'locking' in a particular RNA conformation to inhibit viral protein production suggests a new paradigm for drug design.

Nature Chemical Biology 5, 783 (2009). doi:10.1038/nchembio.247

Author: Jay T Groves

Membrane curvature sensing by amphipathic helices is an emergent property of the ensemble of molecules and membrane sites. New data suggest that individual molecules do not experience stronger binding to curved membranes.

Nature Chemical Biology 5, 784 (2009). doi:10.1038/nchembio.248

Author: Keith Shearwin

Synthetic biologists aim to rationally design and construct useful biological circuits. However, perturbation of host cell physiology, through the very process of turning on an artificial circuit, can give rise to unexpected emergent behaviors, such as bistability.

Conformational inhibition of the hepatitis C virus internal ribosome entry site RNA

Nature Chemical Biology 5, 823 (2009). doi:10.1038/nchembio.217

Authors: Jerod Parsons, M Paola Castaldi, Sanjay Dutta, Sergey M Dibrov, David L Wyles & Thomas Hermann

The internal ribosome entry site (IRES), a highly conserved structured element of the hepatitis C virus (HCV) genomic RNA, is an attractive target for antiviral drugs. Here we show that benzimidazole inhibitors of the HCV replicon act by conformational induction of a widened interhelical angle in the IRES subdomain IIa, which facilitates the undocking of subdomain IIb from the ribosome and ultimately leads to inhibition of IRES-driven translation in HCV-infected cells.