Essex JW
How well does molecular simulation reproduce environment-specific conformations of the intrinsically disordered peptides PLP, TP2 and ONEG?
Intrinsically disordered proteins and peptides (IDPs) do not adopt stable secondary or tertiary structures, and are best structurally characterised as ensembles of flexible conformations.1 While the traditional paradigm holds that biological processes are mediated by macromolecules with fixed three-dimensional structures, it is now becoming increasingly evident that IDPs play a very important role.2 In the absence of a stable structure and characterised by high levels of flexibility, IDPs can easily interconvert between multiple conformations. This enables them to bind to different macromolecules, resulting in diverse functionality.2–6 For example, the intrinsically disordered N-terminal transactivation domain of the protein p53 is structured into a helix upon binding to a hydrophobic cleft in the proteins MDM2 or p300.3,7–9 Similarly the disordered C-terminal region of p53 has been shown to adopt diverse secondary structures when complexed to different protein partners.10 The study of the structural dynamics of IDPs and their participation in protein–protein interactions (PPIs) using computational and experimental studies is increasingly illuminating the subtle yet complex nature of molecular interactions governing biomolecular mechanisms.
ReadHow well does molecular simulation reproduce environment-specific conformations of the intrinsically disordered peptides PLP, TP2 and ONEG?
Intrinsically disordered proteins and peptides (IDPs) do not adopt stable secondary or tertiary structures, and are best structurally characterised as ensembles of flexible conformations.1 While the traditional paradigm holds that biological processes are mediated by macromolecules with fixed three-dimensional structures, it is now becoming increasingly evident that IDPs play a very important role.
ReadComputational Methods and Tools in Antimicrobial Peptide Research
The evolution of antibiotic-resistant bacteria is an ongoing and troubling development that has increased the number of diseases and infections that risk going untreated. There is an urgent need to develop alternative strategies and treatments to address this issue.
ReadThe role of molecular simulations in understanding the mechanisms of cell-penetrating peptides
Cell-penetrating peptides (CPPs) offer an exciting approach to tackle the pharmacokinetic challenges associated with the delivery of large, polar molecules to intracellular targets. Since the discovery of the first CPPs in the early 1990s, vast amounts of research have been undertaken to characterise their cellular uptake mechanisms.
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