The winter holidays are glorious-except when they're not.

The winter holidays are a time to celebrate, but can be oppressive for those who cannot. It is therefore important to look after trainees and colleagues who miss their loved ones on Christmas day. [Image: see text]

Catalytic Redundancies and Conformational Plasticity Drives Selectivity and Promiscuity in Quorum Quenching Lactonases.

Several enzymes from the metallo-β-lactamase-like family of lactonases (MLLs) degrade acyl L-homoserine lactones (AHLs). They play a role in a microbial communication system known as quorum sensing, which contributes to pathogenicity and biofilm formation. Designing quorum quenching () enzymes that can interfere with this communication allows them to be used in a range of industrial and biomedical applications.

Conformational Modulation of a Mobile Loop Controls Catalysis in the (βα)-Barrel Enzyme of Histidine Biosynthesis HisF.

The overall significance of loop motions for enzymatic activity is generally accepted. However, it has largely remained unclear whether and how such motions can control different steps of catalysis. We have studied this problem on the example of the mobile active site βα-loop (loop1) of the (βα)-barrel enzyme HisF, which is the cyclase subunit of imidazole glycerol phosphate synthase.

Mandatory national language requirements in higher education.

Some countries try to curb internationalisation in academia or require that foreign scientists take language courses. While this is done for the wrong reasons, learning the language of the host country has great benefits for academic staff. [Image: see text]

Friends and relatives: insight into conformational regulation from orthologues and evolutionary lineages using KIF and KIN.

Noncovalent interaction networks provide a powerful means to represent and analyze protein structure. Such networks can represent both static structures and dynamic conformational ensembles. We have recently developed two tools for analyzing such interaction networks and generating hypotheses for protein engineering.

In vitro fertilization and the ethics of frozen embryos.

The Alabama Supreme Court decision to consider embryos as children sheds light on a growing problem for IVF clinics: what to do with the increasing number of frozen surplus embryos? [Image: see text]

Catalytic Redundancies and Conformational Plasticity Drives Selectivity and Promiscuity in Quorum Quenching Lactonases.

Several enzymes from the metallo-β-lactamase-like family of lactonases (MLLs) degrade acyl-L-homoserine lactones (AHLs). In doing so, they play a role in a microbial communication system, quorum sensing, which contributes to pathogenicity and biofilm formation. There is currently great interest in designing quorum quenching ( ) enzymes that can interfere with this communication and be used in a range of industrial and biomedical applications.

The ineligibility barrier for international researchers in US academia.

Many grants from US funding agencies are restricted to US citizens or permanent residents which negatively impacts the career options for foreign scientists working in the USA. [Image: see text]

How to write a successful graduate school application.

Practical advice for prospective graduate students on how to apply for a PhD position in the USA and Europe. [Image: see text]

A sensor complements the steric gate when DNA polymerase ϵ discriminates ribonucleotides.

The cellular imbalance between high concentrations of ribonucleotides (NTPs) and low concentrations of deoxyribonucleotides (dNTPs), is challenging for DNA polymerases when building DNA from dNTPs. It is currently believed that DNA polymerases discriminate against NTPs through a steric gate model involving a clash between a tyrosine and the 2'-hydroxyl of the ribonucleotide in the polymerase active site in B-family DNA polymerases. With the help of crystal structures of a B-family polymerase with a UTP or CTP in the active site, molecular dynamics simulations, biochemical assays and yeast genetics, we have identified a mechanism by which the finger domain of the polymerase sense NTPs in the polymerase active site.

Representation matters: responding to the current campaign against DEI efforts.

Abandonment of diversity, equity and inclusion programs undermines fairness and the productivity of research.

Science after Brexit: bright spots on the Horizon?

Is scientific partnership between the UK and EU on the Horizon?

KIF-Key Interactions Finder: A program to identify the key molecular interactions that regulate protein conformational changes.

Simulation datasets of proteins (e.g., those generated by molecular dynamics simulations) are filled with information about how a non-covalent interaction network within a protein regulates the conformation and, thus, function of the said protein.

The perceived decline of "disruptive" science and technology.

The discussion about science's purported loss of disruptive innovation must not distract from the underlying problems that prevent science from deploying its full potential.

Q-RepEx: A Python pipeline to increase the sampling of empirical valence bond simulations.

The exploration of chemical systems occurs on complex energy landscapes. Comprehensively sampling rugged energy landscapes with many local minima is a common problem for molecular dynamics simulations. These multiple local minima trap the dynamic system, preventing efficient sampling.

Scholars in peril: when being a scientist can land you in jail (or worse).

The scientific community needs to speak up loudly to support colleagues who are persecuted and imprisoned for political reasons.

Late-termination of pregnancy for medical reasons: when abortion isn't really by choice.

Repealing Roe vs. Wade and the consequences for medical abortion.

Complex Loop Dynamics Underpin Activity, Specificity, and Evolvability in the (βα) Barrel Enzymes of Histidine and Tryptophan Biosynthesis.

Enzymes are conformationally dynamic, and their dynamical properties play an important role in regulating their specificity and evolvability. In this context, substantial attention has been paid to the role of ligand-gated conformational changes in enzyme catalysis; however, such studies have focused on tremendously proficient enzymes such as triosephosphate isomerase and orotidine 5'-monophosphate decarboxylase, where the rapid (μs timescale) motion of a single loop dominates the transition between catalytically inactive and active conformations. In contrast, the (βα)-barrels of tryptophan and histidine biosynthesis, such as the specialist isomerase enzymes HisA and TrpF, and the bifunctional isomerase PriA, are decorated by multiple long loops that undergo conformational transitions on the ms (or slower) timescale.

Essential Functional Interplay of the Catalytic Groups in Acid Phosphatase.

The cooperative interplay between the functional devices of a preorganized active site is fundamental to enzyme catalysis. An in-depth understanding of this phenomenon is central to elucidating the remarkable efficiency of natural enzymes and provides an essential benchmark for enzyme design and engineering. Here, we study the functional interconnectedness of the catalytic nucleophile (His18) in an acid phosphatase by analyzing the consequences of its replacement with aspartate.

5 suggestions to increase grant application success rates.

A few suggestions and advice to increase the success chances of your grant application.

Adventures on the Routes of Protein Evolution-In Memoriam Dan Salah Tawfik (1955-2021).

Understanding how proteins evolved not only resolves mysteries of the past, but also helps address challenges of the future, particularly those relating to the design and engineering of new protein functions. Here we review the work of Dan S. Tawfik, one of the pioneers of this area, highlighting his seminal contributions in diverse fields such as protein design, high throughput screening, protein stability, fundamental enzyme-catalyzed reactions and promiscuity, that underpin biology and the origins of life.