Neuroendocrine cells like chromaffin cells and PC-12 cells are established models for transport, docking and secretion of secretory vesicles. In micrographs, these vesicles are recognized by their electron dense core. The analysis of secretory vesicle distribution is usually performed manually, which is labour-intensive and subject to human bias and error. We have developed an algorithm to anal...

Prediction of the bound configuration of small-molecule ligands that differ substantially from the cognate ligand of a protein co-crystal structure is much more challenging than re-docking the cognate ligand. Success rates for cross-docking in the range of 20-30 % are common. We present an approach that uses structural information known prior to a particular cutoff-date to make predictions on l...

The main key to success in structure-based drug discovery is the accurate prediction of binding affinities of hit compounds. Molecular docking and scoring functions are often used for this purpose. However, it is often found that the top-ranked docking poses do not represent the right binding mode, and frequently there is no correlation between docking score and biological data. Therefore, “pos...

Library organizations in the Netherlands show an increasing interest to employ depots for low-cost storage and demand fulfillment of item requests. Typically, all libraries organization have a shared catalog, and, on local unavailability, requests can be shipped from elsewhere organization. The depot used consolidate shipment by making tours along libraries, delivering requested items, but also...

Virtual compound screening using molecular docking is widely used in the discovery of new lead compounds for drug design. However, the docking scores are not sufficiently precise to represent the protein-ligand binding affinity. Here, we developed an efficient computational method for calculating protein-ligand binding affinity, which is based on molecular mechanics generalized Born/surface are...

Multi-echelon distribution systems and more precisely, optimization of LTL routes related to them is one of the most popular subjects in the last 5 years of vehicle routing research. Although a plethora of models, methods and visions is found, it is still difficult to compare them because they use different terminologies and some authors insist on the fact there are a multitude of close but dif...

Automated docking of drug-like molecules into receptors is an essential tool in structure-based drug design. While modeling receptor flexibility is important for correctly predicting ligand binding, it still remains challenging. This work focuses on an approach in which receptor flexibility is modeled by explicitly specifying a set of receptor side-chains a-priori. The challenges of this approa...

Docking, the initial association of secretory vesicles with the plasma membrane, precedes formation of the SNARE complex, which drives membrane fusion. For many years, the molecular identity of the docked state, and especially the vesicular docking protein, has been unknown, as has the link to SNARE complex assembly. Here, using adrenal chromaffin cells, we identify the vesicular docking partne...