Detecting Injury Risk Factors with Algorithmic Models in Elite Women's Pathway Cricket.

This exploratory retrospective cohort analysis aimed to explore how algorithmic models may be able to identify important risk factors that may otherwise not have been apparent. Their association with injury was then assessed with more conventional data models. Participants were players registered on the England and Wales Cricket Board women's international development pathway (n=17) from April 2018 to August 2019 aged between 14-23 years (mean 18.

Allosteric mechanisms of nuclear receptors: insights from computational simulations.

The traditional structural view of allostery defines this key regulatory mechanism as the ability of one conformational event (allosteric site) to initiate another in a separate location (active site). In recent years computational simulations conducted to understand how this phenomenon occurs in nuclear receptors (NRs) has gained significant traction. These results have yield insights into allosteric changes and communication mechanisms that underpin ligand binding, coactivator binding site formation, post-translational modifications, and oncogenic mutations.

Generation of receptor structural ensembles for virtual screening using binding site shape analysis and clustering.

Accounting for protein flexibility is an essential yet challenging component of structure-based virtual screening. Whereas an ideal approach would account for full protein and ligand flexibility during the virtual screening process, this is currently intractable using available computational resources. An alternative is ensemble docking, where calculations are performed on a set of individual rigid receptor conformations and the results combined.

Exploring protein flexibility: incorporating structural ensembles from crystal structures and simulation into virtual screening protocols.

The capacity of proteins to adapt their structure in response to various perturbations including covalent modifications, and interactions with ligands and other proteins plays a key role in biological processes. Here, we explore the ability of molecular dynamics (MD), replica exchange molecular dynamics (REMD), and a library of structures of crystal-ligand complexes, to sample the protein conformational landscape and especially the accessible ligand binding site geometry. The extent of conformational space sampled is measured by the diversity of the shapes of the ligand binding sites.

Mechanism of androgen receptor antagonism by bicalutamide in the treatment of prostate cancer.

The androgen receptor (AR) plays a key role in regulating gene expression in a variety of tissues, including the prostate. In that role, it is one of the primary targets in the development of new chemotherapeutics for treatment of prostate cancer and the target of the most widely prescribed current drug, bicalutamide (Bcu), for this disease. In view of its importance, and the absence of a crystal structure for any antagonist--AR complex, we have conducted a series of molecular dynamics-based simulations of the AR--Bcu complex and quantum mechanical (QM) calculations of Bcu, to elucidate the structural basis for antagonism of this key target.