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Relativistic density functional theory (DFT) based molecular dynamical simulations are performed on gold clusters with 3–10 atoms (Au n , n = 3–10) with an aim of understanding their finite temperature behavior. Conformations of a cluster coexisting at different temperatures are analyzed. The simulations reveal that the finite temperature behavior of Au clusters can be classified into three regions, viz., a “solid-like” region, a “structural fluctionality” region, and a “liquid-like” state. The structural fluctionality region is when the cluster dynamically interconverts between two conformations through a metastable intermediate. For Au n , n ≤ 7, where the atoms reorient continuously such that two planar conformations coexist. On the other hand, for Au n , n ≥ 8, the cluster behaves as a quasi-planar liquid where the outer edge atoms of the cluster bend and relax alternatively around a central planar region. In liquid-like state the cluster is predominantly in a 3D conformation and transits through various conformations. The onset and duration of each of the above three regions are seen to be size dependent. Au6 is the most stable cluster and remains in its ground state conformation (or solid-like region) up to nearly 1100 K. Au9 is the least stable among the studied clusters with a liquid-like state around room temperature itself. All the clusters with the exception of Au6 enter the liquid-like state at much lower temperatures as compared to that of bulk gold.

The Ca2+ sensor STIM1 and the Ca2+ channel Orai1 that form the store-operated Ca2+ (SOC) channel complex are key targets for drug development. Selective SOC inhibitors are currently undergoing clinical evaluation for the treatment of auto-immune and inflammatory responses and are also deemed promising anti-neoplastic agents since SOC channels are linked with enhanced cancer cell progression. Here, we describe an investigation of the site of binding of the selective inhibitor Synta66 to the SOC channel Orai1 using docking and molecular dynamics simulations, and live cell recordings. Synta66 binding was localized to the extracellular site close to the transmembrane (TM)1 and TM3 helices and the extracellular loop segments, which, importantly, are adjacent to the Orai1-selectivity filter. Synta66-sensitivity of the Orai1 pore was, in fact, diminished by both Orai1 mutations affecting Ca2+ selectivity and permeation of Na+ in the absence of Ca2+. Synta66 also efficiently blocked SOC in three glioblastoma cell lines but failed to interfere with cell viability, division and migration. These experiments provide new structural and functional insights into selective drug inhibition of the Orai1 Ca2+ channel by a high-affinity pore blocker.

The molecular recognition of carbohydrates by proteins plays a key role in many biological processes including immune response, pathogen entry into a cell, and cell–cell adhesion (e.g., in cancer metastasis). Carbohydrates interact with proteins mainly through hydrogen bonding, metal‐ion‐mediated interaction, and non‐polar dispersion interactions. The role of dispersion‐driven CH–π interactions (stacking) in protein–carbohydrate recognition has been underestimated for a long time considering the polar interactions to be the main forces for saccharide interactions. However, over the last few years it turns out that non‐polar interactions are equally important. In this study, we analyzed the CH–π interactions employing bioinformatics (data mining, structural analysis), several experimental (isothermal titration calorimetry (ITC), X‐ray crystallography), and computational techniques. The Protein Data Bank (PDB) has been used as a source of structural data. The PDB contains over 12 000 protein complexes with carbohydrates. Stacking interactions are very frequently present in such complexes (about 39 % of identified structures). The calculations and the ITC measurement results suggest that the CH–π stacking contribution to the overall binding energy ranges from 4 up to 8 kcal mol−1. All the results show that the stacking CH–π interactions in protein–carbohydrate complexes can be considered to be a driving force of the binding in such complexes.