Cas12a‐based systems, which detect specific nucleic acids via collateral cleavage of reporter DNA, display huge potentials for rapid diagnosis of infectious diseases. Here, the Manganese‐enhanced Cas12a (MeCas12a) system is described, where manganese is used to increase the detection sensitivity up to 13‐fold, enabling the detection of target RNAs as low as five copies. MeCas12a is also highly specific, and is able to distinguish between single nucleotide polymorphisms (SNPs) differing by a single nucleotide. MeCas12a can detect severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in clinical samples and distinguish between SARS‐CoV‐2 and Middle East respiratory syndrome coronavirus (MERS‐CoV) RNA in simulated samples, thus offering an attractive alternative to other methods for the diagnosis of infectious diseases including COVID‐19 and MERS.

Using (hetero)aryl fluorosulfonates as versatile electrophiles, facile on‐DNA cross‐coupling reactions of Suzuki, Sonogashira, and Buchwald are reported here. Notably, all of these reactions show excellent functional group tolerance, mild reaction conditions (relative low temperature and open to air), rich heterocyclic coupling partners, and more importantly, DNA‐compatibility. Thus, these new reactions based on efficient formation of C(sp²)‐C(sp²), C(sp²)‐C(sp), and C(sp²)‐N bonds are highly amenable to synthesis of DNA‐encoded libraries with great molecular diversity.

Microfluidics system enables high-throughput functional screening of antibodies for cancer immunotherapy.

DNA-encoded chemical library (DEL) links the power of amplifiable genetics and the non-self-replicating chemical phenotypes, generating a diverse chemical world. In analogy with the biological world, the DEL world can evolve by using a chemical central dogma, wherein DNA replicates using the PCR reactions to amplify the genetic codes, DNA sequencing transcripts the genetic information, and DNA-compatible synthesis translates into chemical phenotypes. Importantly, DNA-compatible synthesis is the key to expanding the DEL chemical space. Besides, the evolution-driven selection system pushes the chemicals to evolve under the selective pressure, i.e., desired selection strategies. In this perspective, we summarized recent advances in expanding DEL synthetic toolbox and panning strategies, which will shed light on the drug discovery harnessing in vitro evolution of chemicals via DEL.

The function of proteins depends on their ability to sample a variety of states differing in structure and free energy. Deciphering how the various thermally accessible conformations are connected, and understanding their structures and relative energies is crucial in rationalizing protein function. Many biomolecular reactions take place within microseconds to milliseconds, and this timescale is therefore of central functional importance. Here we show that R_1ρ relaxation dispersion experiments in magic‐angle‐spinning solid‐state NMR spectroscopy make it possible to investigate the thermodynamics and kinetics of such exchange process, and gain insight into structural features of short‐lived states.

The large majority of three-dimensional structures of biological macromolecules have been determined by X-ray diffraction of crystalline samples. High-resolution structure determination crucially depends on the homogeneity of the protein crystal. Overall ‘rocking’ motion of molecules in the crystal is expected to influence diffraction quality, and such motion may therefore affect the process of solving crystal structures. Yet, so far overall molecular motion has not directly been observed in protein crystals, and the timescale of such dynamics remains unclear. Here we use solid-state NMR, X-ray diffraction methods and μs-long molecular dynamics simulations to directly characterize the rigid-body motion of a protein in different crystal forms. For ubiquitin crystals investigated in this study we determine the range of possible correlation times of rocking motion, 0.1–100 μs. The amplitude of rocking varies from one crystal form to another and is correlated with the resolution obtainable in X-ray diffraction experiments.