Virtual issue: structure characterization of biomolecules.

Abstract

The structural diversity of biomolecules is quite simply enormous. Although many polymeric biomolecules such as proteins, and ribonucleic (RNA) and deoxyribonucleic (DNA) acids have complex but rather well-defined lowest-energy structures, it became increasingly apparent in recent years that many of them have not. Especially for proteins, but also for RNA, it has been shown that they can instead feature a number of significantly different yet similarly stable structures, or even generally lack defined structure at all, which led to the idea that a static view of single, rigid structures may not be sufficient for understanding the properties and function of biomolecules. This fundamental insight into the dynamic nature of biomolecules, and its highly important implications in folding and binding, only became possible with the use of newly developed or refined experimental approaches. This virtual issue in ChemistryOpen on the “Structure Characterization of Biomolecules” highlights the fruitful interplay between chemical synthesis and advanced techniques for biomolecular characterization in solution and in the gas phase, among them, nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), ion mobility spectrometry (IMS), microscale thermophoresis (MST), and kinetic capillary electrophoresis (KCE). Berezovski and co-workers (DOI: 10.1002/open.201400002) used KCE in combination with MS and IMS to study fast conformational dynamics of DNA G-quadruplexes, and demonstrate that rate and equilibrium constants for DNA folding and metal binding can be determined by KCE-MS. They further show that both drift and migration times in IMS and KCE are different for unfolded and folded, metal-bound DNA. Also concerned with DNA binding is the contribution by Diederichsen and co-workers (DOI: 10.1002/open.201400001), who have synthesized two new compounds, each of which comprises four nucleobase recognition units on a rigid template that is based on a cyclopeptide backbone. Binding of these triostin A analogues was studied by MST, temperature-dependent UV spectroscopy, and MS, which showed evidence for self-aggregation of the TTTT but not the ATTA sequence, and specific binding of the ATTA motif to DNA. The work by Konrat and co-workers (DOI: 10.1002/open.201402008) focuses on magnetic resonance based experimental techniques for the structural characterization of weak and transient protein/protein and protein/RNA complexes. They use sophisticated relaxation dispersion experiments to study lowly populated states of the Escherichia coli cold shock protein CspA complexed to RNA, with detection of either protein or RNA signals, and of the homodimeric complex of an oncogenic protein. Moreover, they introduce a new approach that combines NMR with electron paramagnetic resonance (EPR) spectroscopy to obtain structural information on substates of intrinsically disordered proteins that previously escaped detection by conventional techniques. Sharon and co-workers (DOI: 10.1002/open.201402002) have developed an improved rapid mixing device for time-resolved electrospray ionization (ESI) MS measurements to monitor protein folding, unfolding, and enzymatic reactions. Using cytochrome C as a model system, they demonstrate increased signal-to-noise ratio in ESI mass spectra, and a threefold decrease in experimental repeat error compared to previous capillary mixing devices. This virtual issue in ChemistryOpen on the “Structure Characterization of Biomolecules” highlights the fruitful interplay between chemical synthesis and advanced techniques for biomolecular characterization in solution and in the gas phase… Overall, the contributions in this virtual issue beautifully illustrate the value of combining experimental approaches and techniques for the structural characterization of biomolecules to obtain deeper insight into the dynamic nature and function of proteins, nucleic acids, and their complexes. Priv.-Doz. Dr. Kathrin Breuker Guest Editor Editorial Advisory Board Member ChemistryOpen