There has been huge progress in the discovery of targeted cancer therapies in recent years.
However, even for the most successful and impactful cancer drugs which have been …

Proteins are dynamic entities that undergo a plethora of conformational changes that may
take place on a wide range of time scales. These changes can be as small as the rotation of …

RNA-binding protein TDP-43 mediates essential RNA processing but forms cytoplasmic
neuronal inclusions via its C-terminal domain (CTD) in amyotrophic lateral sclerosis (ALS). It …

Molecular dynamics (MD) and related methods are close to becoming routine computational
tools for drug discovery. Their main advantage is in explicitly treating structural flexibility and …

We review a selection of methods for performing enhanced sampling in molecular dynamics
simulations. We consider methods based on collective variable biasing and on tempering …

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that plays a
critical role in the pathogenesis of many cancers. The structure of intact forms of this receptor …

EGFR mutations account for the majority of druggable targets in lung adenocarcinoma. Over
the past decades the optimization of EGFR inhibitors revolutionized the treatment options for …

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Despite
numerous efforts to target epidermal growth factor receptor (EGFR), commonly dysregulated …

Conspectus This Account highlights recent advances and discusses major challenges in the
field of drug-target recognition, binding, and unbinding studied using metadynamics-based …

A generally applicable metadynamics scheme for predicting the free energy profile of ligand
binding to G-protein-coupled receptors (GPCRs) is described. A common and effective …