The results show clearly that a multi-protease approach allows to improve the identification and molecular characterization of small proteins and SEPs. LC-MS data ProteomeXchange PXD023921.An efficient nickel-catalyzed stereoselective asymmetric intramolecular reductive coupling of N-1,6-alkynones is reported. A P-chiral monophosphine ligand AntPhos was found to be a privileged catalyst for constructing versatile functionalized chiral pyrrolidine rings using triethylsilane as the reducing reagent. Concise synthesis of pyrrolidines with chiral tertiary allylic alcohols was achieved in high yields (99%), excellent stereoselectivity (>991 E/Z), and enantioselectivity (>991 er) with very broad substrate scope. HS-173 Totally, thirty-five N-1,6-alkynones were synthesized and applied in this reaction successfully. This reaction can be scaled up to gram scale without loss of its enantioselectivity. Ligand effects and reaction mechanism are investigated in detail. While the developed asymmetric synthesis of pyrrolidine with chiral tertiary allylic alcohols is anticipated to find wider applications in organic synthesis and chemical biology, the discovered new reactions of N-1,6-alkynone with AntPhos using different catalyst systems would further expanded its new research fields and attract more detailed explorations in the future.Experimentally, the recoil phase leading to rebound behavior for drop impact onto ultrathin oil-covered solid surfaces was studied. It was found that the oil film can rupture during the impact process when the contact angle between the drop liquid and substrate is smaller than 90°. Due to such rupture, the substrate wettability of the substrate can affect the behavior of the drop impact. The rupture of the oil film can be promoted by an increase in impact Weber number (We) and a decrease in the film viscosity and thickness. The effect of We, oil viscosity, and film thickness on the rebound behavior of the drop was also investigated. For low-viscous oil films (5 cSt), it was shown that the smooth and circular edge of the liquid lamella is the key parameter affecting the level of rebound. The smooth rim of the lamella can cause an elongated rebound, while a lamella with a jagged rim will result in a stout rebound. For the impact cases onto oil films with medium and high viscosity, the effects of the film viscosity become more important; the rebound type can be suppressed due to the viscous dispassion. We have also shown that silicone oil can cloak the daughter drops generated in the rebound process for the first time. Due to the existence of the oil, the daughter drops do not merge even when they make contact in the air.Chloroquine (CQ) and hydroxychloroquine (HCQ) have been standard antimalarial drugs since the early 1950s, and very recently, the possibility of their use for the treatment of COVID-19 patients has been considered. To understand the drug mode of action at the submicroscopic level (atoms and molecules), molecular modeling studies with the aid of computational chemistry methods have been of great help. A fundamental step in such theoretical investigations is the knowledge of the predominant drug molecular structure in solution, which is the real environment for the interaction with biological targets. Our strategy to access this valuable information is to perform density functional theory (DFT) calculations of 1H NMR chemical shifts for several plausible molecular conformers and then find the best match with experimental NMR profile in solution (since it is extremely sensitive to conformational changes). Through this procedure, after optimizing 30 trial distinct molecular structures (ωB97x-D/6-31G(d,p)-PCM level of calculation), which may be considered representative conformations, we concluded that the global minimum (named M24), stabilized by an intramolecular N-H hydrogen bond, is not likely to be observed in water, chloroform, and dimethyl sulfoxide (DMSO) solution. Among fully optimized conformations (named M1 to M30, and MD1 and MD2), we found M12 (having no intramolecular H-bond) as the most probable structure of CQ and HCQ in water solution, which is a good approximate starting geometry in drug-receptor interaction simulations. On the other hand, the preferred CQ and HCQ structure in chloroform (and CQ in DMSO-d6) solution was assigned as M8, showing the solvent effects on conformational preferences. We believe that the analysis of 1H NMR data in solution can establish the connection between the macro level (experimental) and the sub-micro level (theoretical), which is not so apparent to us and appears to be more appropriate than the thermodynamic stability criterion in conformational analysis studies.A one-step protocol of the aryl iodine-catalyzed aminolactonization of unactivated alkenes under oxidation conditions was first reported to efficiently construct diverse amino lactones in a short time using HNTs2 as the compatible nitrogen source. In addition, we investigated the influence of the reaction rate based on the structure of the iodoarene precatalyst, which revealed the selective adjustment effect on aminolactonization and oxylactonization. Finally, preliminary experiments verified the feasibility of asymmetric aminolactonization catalyzed by a chiral iodoarene precatalyst.Correlated mutations have played a pivotal role in the recent success in protein fold prediction. Understanding nonadditive effects of mutations is crucial for altering protein structure, as mutations of multiple residues may change protein stability or binding affinity in a manner unforeseen by the investigation of single mutants. While the couplings between amino acids can be inferred from homologous protein sequences, the physical mechanisms underlying these correlations remain elusive. In this work we demonstrate that calculations based on the first-principles of statistical mechanics are capable of capturing the effects of nonadditivities in protein mutations. The identified thermodynamic couplings cover the short-range as well as previously unknown long-range correlations. We further explore a set of mutations in staphyloccocal nuclease to unravel an intricate interaction pathway underlying the correlations between amino acid mutations.