Copper Guanidinoquinoline Complexes as Entatic State Models of Electron-Transfer Proteins.

The electron-transfer abilities of the copper guanidinoquinoline (GUAqu) complexes [Cu(TMGqu)2 ]+/2+ and [Cu(DMEGqu)2 ]+/2+ (TMGqu=tetramethylguanidinoquinoline, DMEGqu=dimethylethylguanidinoquinoline) were examined in different solvents. The determination of the electron self-exchange rate based on the Marcus theory reveals the highest electron-transfer rate of copper complexes with pure N-donor ligands (k11 =1.2×104  s-1 m-1 in propionitrile). This is supported by an examination of the reorganisation energy of the complexes by using Eyring theory and DFT calculations. The low reorganisation energies in nitrile solvents correspond with the high electron-transfer rates of the complexes. Therefore, the [Cu(GUAqu)2 ]+/2+ complexes act as good entatic states model of copper enzymes. The structural influence of the complexes on the kinetic parameters shows that the TMGqu system possesses a higher electron-transfer rate than DMEGqu. Supporting DFT calculations give a closer insight into the kinetics and thermodynamics (Nelsen's four-point method and isodesmic reactions) of the electron transfer.

Multi-level meta-workflows: new concept for regularly occurring tasks in quantum chemistry.

BACKGROUND: In Quantum Chemistry, many tasks are reoccurring frequently, e.g. geometry optimizations, benchmarking series etc. Here, workflows can help to reduce the time of manual job definition and output extraction. These workflows are executed on computing infrastructures and may require large computing and data resources. Scientific workflows hide these infrastructures and the resources needed to run them. It requires significant efforts and specific expertise to design, implement and test these workflows. SIGNIFICANCE: Many of these workflows are complex and monolithic entities that can be used for particular scientific experiments. Hence, their modification is not straightforward and it makes almost impossible to share them. To address these issues we propose developing atomic workflows and embedding them in meta-workflows. Atomic workflows deliver a well-defined research domain specific function. Publishing workflows in repositories enables workflow sharing inside and/or among scientific communities. We formally specify atomic and meta-workflows in order to define data structures to be used in repositories for uploading and sharing them. Additionally, we present a formal description focused at orchestration of atomic workflows into meta-workflows. CONCLUSIONS: We investigated the operations that represent basic functionalities in Quantum Chemistry, developed the relevant atomic workflows and combined them into meta-workflows. Having these workflows we defined the structure of the Quantum Chemistry workflow library and uploaded these workflows in the SHIWA Workflow Repository.Graphical AbstractMeta-workflows and embedded workflows in the template representation.

Portals and Web-Based Resources for Virtual Screening.

Virtual screening for active compounds has become an essential step within the drug development pipeline. The computer based prediction of compound binding modes is one of the most time and cost efficient methods for screening ligand libraries and enrich results of potential drugs. Here we present an overview about currently available online resources regarding compound databases, docking applications, and science gateways for drug discovery and virtual screening, in order to help structural biologists in choosing the best tools for their analysis. The appearance of the user interface, authentication and security aspects, data management, and computational performance will be discussed. We anticipate a broad overview about currently available solutions, guiding computational chemists and users from related fields towards scientifically reliable results.

Insights into the influence of dispersion correction in the theoretical treatment of guanidine-quinoline copper(I) complexes.

For the description of steric effects, dispersion correction is important in density functional theory. By investigation of sterically encumbered guanidine-quinoline copper bis(chelate) complexes, we could show that the correct description requires modern dispersion correction using Becke-Johnson (BJ) damping and that earlier dispersion corrections are not sufficient. The triple-zeta basis set def2-TZVP of the Ahlrichs series is balanced and converged for the structural description. With regard to functionals, the best structural description is obtained with the TPSSh functional but B3LYP is very suited as well. Cutting of ligand substituents leads to distortions which limit the predictive ability of such calculations. We recommend the calculation of "full" chemical systems with inclusion of dispersion correction using BJ damping. In the further analysis of the regarded copper bis(chelate) complexes, we found that the theoretical description of optical and Raman spectra is not much affected by the dispersion although charge transfer excitations come into play and that B3LYP/def2-TZVP is the best choice. Hence, we can derive the result that the correct structural description with dispersion serves as crucial basis for subsequent calculation steps.

Performance studies on distributed virtual screening.

Virtual high-throughput screening (vHTS) is an invaluable method in modern drug discovery. It permits screening large datasets or databases of chemical structures for those structures binding possibly to a drug target. Virtual screening is typically performed by docking code, which often runs sequentially. Processing of huge vHTS datasets can be parallelized by chunking the data because individual docking runs are independent of each other. The goal of this work is to find an optimal splitting maximizing the speedup while considering overhead and available cores on Distributed Computing Infrastructures (DCIs). We have conducted thorough performance studies accounting not only for the runtime of the docking itself, but also for structure preparation. Performance studies were conducted via the workflow-enabled science gateway MoSGrid (Molecular Simulation Grid). As input we used benchmark datasets for protein kinases. Our performance studies show that docking workflows can be made to scale almost linearly up to 500 concurrent processes distributed even over large DCIs, thus accelerating vHTS campaigns significantly.

The MoSGrid Science Gateway - A Complete Solution for Molecular Simulations.

The MoSGrid portal offers an approach to carry out high-quality molecular simulations on distributed compute infrastructures to scientists with all kinds of background and experience levels. A user-friendly Web interface guarantees the ease-of-use of modern chemical simulation applications well established in the field. The usage of well-defined workflows annotated with metadata largely improves the reproducibility of simulations in the sense of good lab practice. The MoSGrid science gateway supports applications in the domains quantum chemistry (QC), molecular dynamics (MD), and docking. This paper presents the open-source MoSGrid architecture as well as lessons learned from its design.

Workflow-enhanced conformational analysis of guanidine zinc complexes via a science gateway.

The new science gateway MoSGrid (Molecular Simulation Grid) enables users to submit and process molecular simulation studies on a large scale. A conformational analysis of guanidine zinc complexes, which are active catalysts in the ring-opening polymerization of lactide, is presented as an example. Such a large-scale quantum chemical study is enabled by workflow technologies. Two times 40 conformers have been generated, for two guanidine zinc complexes. Their structures were optimized using Gaussian03 and the energies processed within the quantum chemistry portlet of the MoSGrid portal. All meta- and post-processing steps have been performed in this portlet. All workflow features are implemented via WS-PGRADE and submitted to UNICORE.