Volume 9 Issue 3, March 2017

Volume 9 Issue 3

Although thermodynamic-based methods such as molecular docking have been very effective in the virtual screening of drug candidates, new approaches that will improve the success rate of computer-aided, structure-based drug design are still sought. Xavier Barril and colleagues have now developed a screening method based on structural — rather than thermodynamic — stability that is complementary to existing methods. Their approach uses dynamic undocking (DUck): a fast computational method to calculate the work necessary to break the most important contact with the receptor. The potential of the combination of docking and undocking strategies is demonstrated by screening a diverse set of molecules against the molecular chaperone and oncology target Hsp90 (as stylized on the cover).Article p201IMAGE: SERGIO RUIZ-CARMONA, UNIVERSITY OF BARCELONACOVER DESIGN: LAUREN HESLOP

News and Views

  • News & Views |

    Planar molecules may break mirror symmetry when aligned on a surface, but both right- and left-handed forms will be created. Starting with a single-handed precursor, chiral adsorbates of planar hydrocarbons with a single handedness are formed in on-surface reactions.

    • Karl-Heinz Ernst
  • News & Views |

    The process of electronic energy transfer between molecules has long fascinated chemists. Femtosecond spectroscopy measurements of a series of molecular dimers now reveal signals that arise from non-Born–Oppenheimer coupling, suggesting a new mechanism to enhance energy transfer.

    • Daniel B. Turner
  • News & Views |

    Free radicals are notorious for unselective coupling reactions; however, the coupling of free radicals generated from acyl tellurides has now been shown to form C–C bonds with remarkable fidelity, which enables easy one-step assembly of densely oxygenated natural product motifs.

    • Wenhao Zhang
    •  & Ang Li


  • Article |

    Structure-based drug design has generally focused on calculating binding free energies of protein–ligand complexes. It has now been shown that structural, rather than thermodynamic, stability — specifically, the work necessary to reach a quasi-bound state in which the ligand has just broken the most important contact with the receptor — can be calculated and used as a tool in virtual screening.

    • Sergio Ruiz-Carmona
    • , Peter Schmidtke
    • , F. Javier Luque
    • , Lisa Baker
    • , Natalia Matassova
    • , Ben Davis
    • , Stephen Roughley
    • , James Murray
    • , Rod Hubbard
    •  & Xavier Barril
  • Article |

    Pentoses and hexoses represent important structural motifs in bioactive secondary metabolites, though their synthesis often requires several elongation steps. Now, a method for radical–radical coupling reactions of sugar derivatives enables the single-step preparation of the oxygenated carbon chains of several natural products, including sagittamide D, maitotoxin and hikizimycin.

    • Kengo Masuda
    • , Masanori Nagatomo
    •  & Masayuki Inoue
  • Article |

    Flat, prochiral molecules form chiral adsorbates on achiral surfaces, but such assemblies are globally racemic. Now, it is shown that this mirror symmetry can be broken through stereocontrolled on-surface synthesis. Enantiopure helicene molecules can be transformed into flat, enantiofacially adsorbed products through a cascade of reactions on Ag(111) monitored by high-resolution scanning probe microscopy.

    • Oleksandr Stetsovych
    • , Martin Švec
    • , Jaroslav Vacek
    • , Jana Vacek Chocholoušová
    • , Andrej Jančařík
    • , Jiří Rybáček
    • , Krzysztof Kosmider
    • , Irena G. Stará
    • , Pavel Jelínek
    •  & Ivo Starý
  • Article |

    Synthetic heterodimers provide a platform to demonstrate molecular design principles of vibronic coupling. Now, it has been shown that quantum beating caused by vibronic coupling can be controlled by packing a structurally flexible heterodimer on single-walled carbon nanotubes. This quantum beating requires a vibration to be resonant with the energy gap between excited states and structural rigidity.

    • Lili Wang
    • , Graham B. Griffin
    • , Alice Zhang
    • , Feng Zhai
    • , Nicholas E. Williams
    • , Richard F. Jordan
    •  & Gregory S. Engel
  • Article |

    Stereodynamics describes how the vector properties of molecules affect the probabilities of specific processes in molecular collisions. Measurements of irregular diffraction patterns for NO radicals colliding with rare-gas atoms reveal a previously unrecognized type of quantum stereodynamics and a ‘propensity rule’ for the magnetic quantum number (m) of the molecules.

    • Jolijn Onvlee
    • , Sean D. S. Gordon
    • , Sjoerd N. Vogels
    • , Thomas Auth
    • , Tijs Karman
    • , Bethan Nichols
    • , Ad van der Avoird
    • , Gerrit C. Groenenboom
    • , Mark Brouard
    •  & Sebastiaan Y. T. van de Meerakker
  • Article |

    A chemical proteomic strategy is described for the discovery of protein-bound electrophilic groups in human cells. Using this approach, the dynamic regulation of the pyruvoyl catalytic cofactor in S-adenosyl-L-methionine decarboxylase was characterized and an N-terminal glyoxylyl modification on secernin proteins was discovered.

    • Megan L. Matthews
    • , Lin He
    • , Benjamin D. Horning
    • , Erika J. Olson
    • , Bruno E. Correia
    • , John R. Yates III
    • , Philip E. Dawson
    •  & Benjamin F. Cravatt
  • Article |

    Isolating nanoscale species in liquids permits their scalable manipulation, enabling numerous fundamental and applied processes. Thus, achieving true dissolution of 2D materials is particularly desirable. Now, ionic salts of a range of important layered materials have been shown to spontaneously dissolve, yielding solutions of charged, monodisperse, undamaged and easy-to-manipulate 2D nanosheets.

    • Patrick L. Cullen
    • , Kathleen M. Cox
    • , Mohammed K. Bin Subhan
    • , Loren Picco
    • , Oliver D. Payton
    • , David J. Buckley
    • , Thomas S. Miller
    • , Stephen A. Hodge
    • , Neal T. Skipper
    • , Vasiliki Tileli
    •  & Christopher A. Howard
  • Article |

    Switching the chirality of helicates non-invasively is challenging, even though helicates were discovered some decades ago. Now, by incorporating a light-driven molecular motor into a Cu(I)-helicate, the chirality of the metal helicate as well as the assembly and disassembly processes can be switched non-invasively by light and heat.

    • Depeng Zhao
    • , Thomas van Leeuwen
    • , Jinling Cheng
    •  & Ben L. Feringa
  • Article |

    Despite decades of research into heme-copper oxidases, the advantages provided by copper over iron as the non-heme metal has remained unclear. Now, the preference of copper over iron has finally been explained. Copper favours faster electron transfer and higher O–O bond activation, which results in much higher oxidase activity than would be achieved by an iron equivalent.

    • Ambika Bhagi-Damodaran
    • , Matthew A. Michael
    • , Qianhong Zhu
    • , Julian Reed
    • , Braddock A. Sandoval
    • , Evan N. Mirts
    • , Saumen Chakraborty
    • , Pierre Moënne-Loccoz
    • , Yong Zhang
    •  & Yi Lu
  • Article |

    Anti-proliferative compounds that display enhanced toxicity in a low-oxygen (hypoxic) environment may be used to eradicate aggressive and therapy-resistant cancer cells. Now, a promising lead structure has been identified in the BE-43547-class of depsipeptide natural products.

    • Nikolaj L. Villadsen
    • , Kristian M. Jacobsen
    • , Ulrik B. Keiding
    • , Esben T. Weibel
    • , Bjørn Christiansen
    • , Thomas Vosegaard
    • , Morten Bjerring
    • , Frank Jensen
    • , Mogens Johannsen
    • , Thomas Tørring
    •  & Thomas B. Poulsen
  • Article |

    Ultrafast 2D Raman-THz spectroscopy has been applied to investigate the dynamics of the hydrogen-bond networks in aqueous salt solutions. It was demonstrated that the degree of inhomogeneity of the intermolecular modes of the liquid correlates with the structure-making capability of the cation.

    • Andrey Shalit
    • , Saima Ahmed
    • , Janne Savolainen
    •  & Peter Hamm
  • Article |

    Reversible fluorescent probes for intracellular glutathione (GSH) imaging have now been designed and synthesized based on Si-rhodamine fluorophores. These probes are shown to be capable of quantifying the GSH concentration in various living cell types and also for monitoring real-time live-cell imaging of GSH dynamics with a temporal resolution of seconds.

    • Keitaro Umezawa
    • , Masafumi Yoshida
    • , Mako Kamiya
    • , Tatsuya Yamasoba
    •  & Yasuteru Urano
  • Article |

    Biomolecular nanoscale compartments are ubiquitous in living systems. Although their formation is fairly straightforward, the same cannot be said of their inorganic counterparts. In this study, uniform nanoshells are observed self-assembling from stabilizer-free inorganic nanoparticles in water, under ambient conditions, and without the need for spherical tiling. This enables further study of inorganic prebiotic systems and compartmentalized biomimetic catalysis.

    • Ming Yang
    • , Henry Chan
    • , Gongpu Zhao
    • , Joong Hwan Bahng
    • , Peijun Zhang
    • , Petr Král
    •  & Nicholas A. Kotov

In Your Element

  • In Your Element |

    Made under a cloak of wartime secrecy, yet announced in the most public of ways — a radioactive element that governments insist we take into our homes. Ben Still explains how element 95 is one of real contradiction.

    • Ben Still