The OPEP coarse-grained protein model has been applied to a wide range of applications since its first release 15 years ago. The model, which combines energetic and structural accuracy and chemical specificity, allows the study of single protein properties, DNA-RNA complexes, amyloid fibril formation and protein suspensions in a crowded environment. Here we first review the current state of the model and the most exciting applications using advanced conformational sampling methods. We then present the current limitations and a perspective on the ongoing developments.

Although RNAs play many cellular functions, little is known about the dynamics and thermodynamics of these molecules. In principle, all-atom molecular dynamics simulations can investigate these issues, but with current computer facilities, these simulations have been limited to small RNAs and to short times. HiRe-RNA, a recently proposed high-resolution coarse-grained RNA that captures many geometric details such as base pairing and stacking, is able to fold RNA molecules to near-native structures in a short computational time. So far, it had been applied to simple hairpins, and here we present its application to duplexes of a couple dozen nucleotides and show how with replica exchange molecular dynamics (REMD) we can easily predict the correct double helix from a completely random configuration and study the dissociation curve. To show the versatility of our model, we present an application to a double stranded DNA molecule as well. A reconstruction algorithm allows us to obtain full atom structures from the coarse-grained model. Through atomistic molecular dynamics (MD), we can compare the dynamics starting from a representative structure of a low temperature replica or from the experimental structure, and show how the two are statistically identical, highlighting the validity of a coarse-grained approach for structured RNAs and DNAs.

BackgroundNormal mode analysis (NMA) using elastic network models is a reliable and cost-effective computational method to characterise protein flexibility and by extension, their dynamics. Further insight into the dynamics–function relationship can be gained by comparing protein motions between protein homologs and functional classifications. This can be achieved by comparing normal modes obtained from sets of evolutionary related proteins.ResultsWe have developed an automated tool for comparative NMA of a set of pre-aligned protein structures. The user can submit a sequence alignment in the FASTA format and the corresponding coordinate files in the Protein Data Bank (PDB) format. The computed normalised squared atomic fluctuations and atomic deformation energies of the submitted structures can be easily compared on graphs provided by the web user interface. The web server provides pairwise comparison of the dynamics of all proteins included in the submitted set using two measures: the Root Mean Squared Inner Product and the Bhattacharyya Coefficient. The Comparative Analysis has been implemented on our web server for NMA, WEBnm@, which also provides recently upgraded functionality for NMA of single protein structures. This includes new visualisations of protein motion, visualisation of inter-residue correlations and the analysis of conformational change using the overlap analysis. In addition, programmatic access to WEBnm@ is now available through a SOAP-based web service. Webnm@ is available at http://apps.cbu.uib.no/webnma.ConclusionWEBnm@ v2.0 is an online tool offering unique capability for comparative NMA on multiple protein structures. Along with a convenient web interface, powerful computing resources, and several methods for mode analyses, WEBnm@ facilitates the assessment of protein flexibility within protein families and superfamilies. These analyses can give a good view of how the structures move and how the flexibility is conserved over the different structures.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-014-0427-6) contains supplementary material, which is available to authorized users.

HiRE-RNA is a coarse-grained model for RNA structure prediction and the dynamical study of RNA folding. Using a reduced set of particles and detailed interactions accounting for base-pairing and stacking, we show that noncanonical and multiple base interactions are necessary to capture the full physical behavior of complex RNAs. In this paper, we give a full account of the model and present results on the folding, stability, and free energy surfaces of 16 systems with 12 to 76 nucleotides of increasingly complex architectures, ranging from monomers to dimers, using a total of 850 μs of simulation time.

Summary: The volume of an internal protein pocket is fundamental to ligand accessibility. Few programs that compute such volumes manage dynamic data from molecular dynamics (MD) simulations. Limited performance often prohibits analysis of large datasets. We present Epock, an efficient command-line tool that calculates pocket volumes from MD trajectories. A plugin for the VMD program provides a graphical user interface to facilitate input creation, run Epock and analyse the results.Availability and implementation: Epock C++ source code, Python analysis scripts, VMD Tcl plugin, documentation and installation instructions are freely available at http://epock.bitbucket.org.Contact: benoist.laurent@gmail.com or baaden@smplinux.deSupplementary information: Supplementary data are available at Bioinformatics online.

Ion mobility coupled to mass spectrometry (IM-MS) is widely used to study protein dynamics and structure in the gas phase. Increasing the energy with which the protein ions are introduced to the IM cell can induce them to unfold, providing information on the comparative energetics of unfolding between different proteoforms. Recently, a high-resolution cyclic IM-mass spectrometer (cIM-MS) was introduced, allowing multiple, consecutive tandem IM experiments (IM n ) to be carried out. We describe a tandem IM technique for defining detailed protein unfolding pathways and the dynamics of disordered proteins. The method involves multiple rounds of IM separation and collision activation (CA): IM-CA-IM and CA-IM-CA-IM. Here, we explore its application to studies of a model protein, cytochrome C, and dimeric human islet amyloid polypeptide (hIAPP), a cytotoxic and amyloidogenic peptide involved in type II diabetes. In agreement with prior work using single stage IM-MS, several unfolding events are observed for cytochrome C. IM n -MS experiments also show evidence of interconversion between compact and extended structures. IM n -MS data for hIAPP shows interconversion prior to dissociation, suggesting that the certain conformations have low energy barriers between them and transition between compact and extended forms.

Structural determination of molecular complexes by cryo-EM requires large, often complex processing of the image data that are initially obtained. Here, TEMPy2, an update of the TEMPy package to process, optimize and assess cryo-EM maps and the structures fitted to them, is described. New optimization routines, comprehensive automated checks and workflows to perform these tasks are described.

Structures of seven CASP13 targets were determined using cryo‐electron microscopy (cryo‐EM) technique with resolution between 3.0 and 4.0 Å. We provide an overview of the experimentally derived structures and describe results of the numerical evaluation of the submitted models. The evaluation is carried out by comparing coordinates of models to those of reference structures (CASP‐style evaluation), as well as checking goodness‐of‐fit of modeled structures to the cryo‐EM density maps. The performance of contributing research groups in the CASP‐style evaluation is measured in terms of backbone accuracy, all‐atom local geometry and similarity of inter‐subunit interfaces. The results on the cryo‐EM targets are compared with those on the whole set of eighty CASP13 targets. A posteriori refinement of the best models in their corresponding cryo‐EM density maps resulted in structures that are very close to the reference structure, including some regions with better fit to the density.