Mechanistic Insights into the Cofactor Binding Dynamics and Interaction between Telmisartan and Human Thiopurine S-Methyltransferase.

Thiopurine S-methyltransferase (TPMT) is crucial for catalyzing the inactivation and reducing the toxicity of thiopurine class of immunosuppressive drugs which are FDA-approved to treat autoimmune diseases and transplant rejection. Its complete or partial loss of activity during standard-dose thiopurine treatment causes severe bone marrow suppression and death. Therefore, FDA recommends testing TPMT activity to identify patients at high risk of developing life-threatening complications.

Novel Insights Into the Dynamic Conformational Transitions and Active Site Plasticity of Human Immunoregulatory Cathepsin S.

Cathepsin S (CatS), a cysteine protease, catalyzes the cleavage of immunoregulatory peptides and mediates tissue destruction in autoimmune and inflammatory diseases. Plasticity of its ligand binding site and mechanisms of dynamic transitions between different conformational states are critical in drug discovery; however, knowledge of its entire conformational landscape and transition mechanisms remains incomplete. Therefore, we investigated the atomic-level interactions between active site cleft residues that contribute to its structural and functional plasticity.

The developmental and inflammatory disease target protein ADAM17 is vulnerable to off-target interaction by the drug eltrombopag: Insights from molecular modeling.

The loss of proteolytic activity of ADAM17 causes birth defects and embryonic lethality. Conversely, inhibiting ADAM17 activity represents a potential strategy for treating inflammatory and autoimmune diseases. ADAM17 has an active site cleft with a divalent Zn ion and hydrophobic S1'/S3' subsites interconnected to form an L shaped cavity.

Dynamic bandgap modulation in CsPbBr perovskite nanocrystals through reversible ammonia intercalation.

Modulation of the electronic states of a semiconductor is an intriguing area of research because of its interesting applications. In general, physical methods are used to reversibly manipulate the bandgap of semiconductors. Herein, we have used a simple molecule, ammonia, and allowed it to intercalate inside the crystal lattice of CsPbBr perovskites to alter the band positions.

Probing the Structural Degradation of CsPbBr Perovskite Nanocrystals in the Presence of HO and HS: How Weak Interactions and HSAB Matter.

Structural degradation of all inorganic CsPbBr in the presence of moisture is considered as one of its major limitations to use as an active component in various light-harvesting and light-emitting devices. Herein, we used two similar molecules, HO and HS, with similar structures, to follow the decomposition mechanism of CsPbBr perovskite nanocrystals. Interestingly, HO acts as a catalyst for the decomposition of CsPbBr, which is in contrast to HS.

Biomolecular interactions between the antibacterial ceftolozane and the human inflammatory disease target ADAM17: a drug repurposing study.

Inhibition of a disintegrin and metalloproteinase-17 (ADAM17), a metzincin, is proposed as a novel therapeutic strategy to suppress overproduction of the proinflammatory cytokine TNF-α in rheumatoid arthritis and inflammatory bowel disease. Existing ADAM17 inhibitors generate toxic metabolites or haven't progressed in clinical trials. Previous studies suggest that ligands which bind to ADAM17 active site by interacting with the Zn ion and L-shaped hydrophobic S1'- and S3'-pockets and forming favorable hydrogen bonds could act as potential ADAM17 inhibitors.

Structures and chemical properties of silicene: unlike graphene.

The discovery of graphene and its remarkable and exotic properties have aroused interest in other elements and molecules that form 2D atomic layers, such as metal chalcogenides, transition metal oxides, boron nitride, silicon, and germanium. Silicene and germanene, the Si and Ge counterparts of graphene, have interesting fundamental physical properties with potential applications in technology. For example, researchers expect that silicene will be relatively easy to incorporate within existing silicon-based electronics.

Tip enhanced Raman spectroscopy (TERS) as a probe for the buckling distortion in silicene.

Silicene, the all-Si analogue of graphene, is symmetrically buckled in each of the six-membered units and this buckling is periodically translated across the surface. Raman spectra of silicene clusters were calculated using first principles DFT methods to explore the intrinsic buckling in silicene. The presence of metal clusters as a tip over the silicene units affects the intensity of the buckling modes which can be enhanced by increasing the number of atoms in the clusters.

Molecular Balances Based on Aliphatic CH-π and Lone-Pair-π Interactions.

CH···π and lone-pair···π interactions are estimated for a series of conformationally dynamic bicyclic N-aryliimides. On the basis of their strengths and mutual synergy/competition, the molecules prefer a folded/unfolded conformation. Calculations suggest strategies to selectively isolate the folded form by increasing the strength of the attractive CH···π interaction or removing the lone-pair···π repulsion.

Structures and electronic properties of silicene clusters: a promising material for FET and hydrogen storage.

Structures and electronic properties of clusters of an all-Si analogue of graphene, silicene, have been studied through quantum chemical calculations. The structures of the six-membered rings show interesting chair like puckering, which for large sheet-like clusters form ordered ripples. Binding energies, HOMO-LUMO gaps and polarizabilities for the silicene clusters show interesting monotonic trends analogous to polyacenes.