Mass spectrometry is an essential analytical technique for high-throughput analysis in proteomics and metabolomics. The development of new separation techniques, precise mass analyzers and experimental protocols is a very active field of research. This leads to more complex experimental setups yielding ever increasing amounts of data. Consequently, analysis of the data is currently often the bottleneck for experimental studies. Although software tools for many data analysis tasks are available today, they are often hard to combine with each other or not flexible enough to allow for rapid prototyping of a new analysis workflow. We present OpenMS, a software framework for rapid application development in mass spectrometry. OpenMS has been designed to be portable, easy-to-use and robust while offering a rich functionality ranging from basic data structures to sophisticated algorithms for data analysis. This has already been demonstrated in several studies. OpenMS is available under the Lesser GNU Public License (LGPL) from the project website at http://www.openms.de .

Negatively charged globular proteins in solution undergo a condensation upon adding trivalent counterions between two critical concentrations ${\mathrm{C}}^{*}$ and ${\mathrm{C}}^{**}$, ${\mathrm{C}}^{*}<{\mathrm{C}}^{**}$. This reentrant condensation behavior above ${\mathrm{C}}^{**}$ is caused by short-ranged electrostatic interactions between multivalent cations and acidic residues, mechanistically different from the case of DNA. Small-angle x-ray scattering indicates a short-ranged attraction between counterion-bound proteins near ${\mathrm{C}}^{*}$ and ${\mathrm{C}}^{**}$. Monte Carlo simulations (under these strong electrostatic coupling conditions) support an effective inversion of charge on surface side chains through binding of the multivalent counterions.

The combination of Reverse Transcription (RT) and high-throughput sequencing has emerged as a powerful combination to detect modified nucleotides in RNA via analysis of either abortive RT-products or of the incorporation of mismatched dNTPs into cDNA. Here we simultaneously analyze both parameters in detail with respect to the occurrence of N-1-methyladenosine (m¹A) in the template RNA. This naturally occurring modification is associated with structural effects, but it is also known as a mediator of antibiotic resistance in ribosomal RNA. In structural probing experiments with dimethylsulfate, m¹A is routinely detected by RT-arrest. A specifically developed RNA-Seq protocol was tailored to the simultaneous analysis of RT-arrest and misincorporation patterns. By application to a variety of native and synthetic RNA preparations, we found a characteristic signature of m¹A, which, in addition to an arrest rate, features misincorporation as a significant component. Detailed analysis suggests that the signature depends on RNA structure and on the nature of the nucleotide 3′ of m¹A in the template RNA, meaning it is sequence dependent. The RT-signature of m¹A was used for inspection and confirmation of suspected modification sites and resulted in the identification of hitherto unknown m¹A residues in trypanosomal tRNA.

The accurate modeling of the dielectric properties of water is crucial for many applications in physics, computational chemistry, and molecular biology. This becomes possible in the framework of nonlocal electrostatics, for which we propose a novel formulation allowing for numerical solutions for the nontrivial molecular geometries arising in the applications mentioned before. Our approach is based on the introduction of a secondary field psi, which acts as the potential for the rotation free part of the dielectric displacement field D. For many relevant models, the dielectric function of the medium can be expressed as the Green's function of a local differential operator. In this case, the resulting coupled Poisson (-Boltzmann) equations for psi and the electrostatic potential phi reduce to a system of coupled partial differential equations. The approach is illustrated by its application to simple geometries.