The median salary rose to $120,000, with higher wages in New England and on the West Coast as well as in chemical engineering

What went wrong in the world of science

A plutonium-packed generator disappeared on one of the world’s highest mountains in a covert mission that the U.S. will not talk about.

Accumulating evidence has connected the chemically unstable, DNA-damaging gut bacterial natural product colibactin to colorectal cancer, including the identification of mutational signatures that are ...

From the onset of fundamental statistical mechanical constructs formulated in the late 19th century, alchemical free-energy methods slowly emerged and transitioned to become operational tools of biomolecular simulation applicable to a wide range of problems including protein–ligand binding for drug discovery research. This article reconstructs how statistical mechanical approaches such as thermodynamic integration and free-energy perturbation were reconfigured in the early 1980s to address the complexities of increasingly heterogeneous biomolecular systems. Drawing on oral history interviews and primary literature, the study examines the technical, institutional, theoretical, and infrastructural conditions under which these methods were implemented, and it became progressively operational. These conditions encompassed the consolidation of lab-specific software infrastructures, the formulation of practical simulation protocols, and essential statistical mechanical clarifications. From this perspective, the progress of free-energy methods proceeded less from a unified convergence than from an iterative troubleshooting process of alignment involving practical and theoretical considerations. The aim of the present article is to offer a historically grounded account of how free-energy techniques acquired practical and functional reliability.

We report the results of experiments to test the hypothesis that binding energy from the adenosine diphosphate (ADP) fragment of the NAD+ cofactor is utilized to drive a protein conformational change...

Cooperative gas adsorption in metal–organic frameworks (MOFs) is a rare phenomenon that generally involves long-range communication between multiple binding sites. We demonstrate a MOF containing coba...

Nature - From NASA to the National Institutes of Health, federal agencies conduct research that universities cannot. Agency scientists speak out about the irreplaceable facilities, institutional...

Some doctoral programmes are admitting no students at all amid uncertainty about federal science funding.

X-succinate synthases (XSSs) are a class of glycyl radical enzymes (GREs) that enable anaerobic hydrocarbon functionalization, granting anaerobes access to petroleum-derived substrates for metabolism. Owing to their ability to functionalize components of crude oil and catalyze selective olefin hydroalkylation, XSSs hold significant biotechnological promise. However, mechanistic understanding has been limited due to long-standing barriers to installing their essential glycyl radical in vitro, which have only recently been overcome. Unlike most GREs, XSSs contain accessory subunits that bind to the periphery of the catalytic subunit. The most well-studied XSS, benzylsuccinate synthase (BSS), includes two [4Fe–4S] cluster-binding accessory subunits, BSSγ and BSSβ. The full structure of BSSγ and the catalytic role of BSSβ have remained unclear. Here, we report the crystal structure of BSSγ with its [4Fe–4S] cluster intact, revealing a HiPP-like fold similar to that of BSSβ. Through biochemical and spectroscopic studies, we provide evidence that BSSβ promotes thiyl radical formation, even in the absence of a substrate. This finding contrasts with recent models, in which substrate binding is required to trigger thiyl radical formation. With this mechanistic insight, we optimized reaction conditions to achieve total turnover numbers of ∼17,000, representing an over 340-fold improvement compared to prior reports. We further show that in the absence of BSSβ, activated BSSαγ remains catalytically active for up to 11 days. Together, these results clarify the unique regulatory architecture of BSS and lay the groundwork for the use of XSSs in biocatalytic applications.