Featured publication: Long and large simulation of a megadalton peptide cage – implications for design.

Our manuscript entitled, “The dynamical interplay between a megadalton peptide nanocage and solutes probed by microsecond atomistic MD; implications for design”  has been accepted for publication in Physical Chemistry Chemical Physics (PCCP), (2018), DOI: 10.1039/c8cp06282j. Deborah K. Shoemark, Amaurys Avila Ibarra, James F. Ross, Joseph L. Beesley, Harriet E.V. Bray, Majid Mosayebi, Noah Linden, Tanniemola B. Liverpool, Simon N. McIntosh-Smith, Derek N. Woolfson and Richard B. Sessions.

Here we present the lessons learnt from performing atomistic simulations of 0.6 – 1 microseconds of three ~42 million atom peptide nanocage (SAGE) systems, with and without protein and small molecule solutes. Using GROMACS and the UK supercomputer Archer, data were collected over 2 years. Detailed analysis reveals the structural integrity/helical stability of the SAGEs themselves, how SAGEs interact with the proteins and small molecule species in the systems, whether contact with SAGE influences the native fold of solute proteins and how frequently solutes or ions pass through pores in the SAGEs. Knowing how and where to elaborate and/or modify the SAGE building blocks is important to inform the design process for this synthetic biological approach to diverse applications.  As a vaccine delivery platform, SAGEs that are modular and reproducible, could be tailored to respond to emerging infectious threats more rapidly than conventional methods. For targeted drug delivery, adding peptides that bind SAGEs packed with drug, to specific cell types could reduce dosage demand and side-effects. As nanoreactors for complex chemistry, encapsulating enzyme pathways may allow for more efficient and environmentally friendly catalysis.


BcompB seminar 18/09/2018: Dr Richard Sessions

Dr Richard Sessions is the molecular modeller responsible for the development of the docking algorithm BUDE (Bristol University Docking engine), the binding energy prediction method that underpins programs such as CC-builder, Isambard and Poppi.

His talk tomorrow explores the fundamental question, “Why do molecules stick together?”

It will be at 2pm in C42 in the Biomedical Sciences building.


Featured publication: modelling compliments experiment for finding new smoking cessation drugs


Below is a link to the press release for a paper that provides an example of how modelling can compliment experimental techniques in the quest for new or improved drug candidates. In this case the subjects are the nicotinic acetylcholine receptor (nAchR) subtypes associated with smoking addiction pathways. Selective binding of drugs to inhibit or partially antagonise the alpha4/beta2 subtypes is believed to increase the efficacy and decrease side-effects of smoking cessation therapies such as Varenicline, targeting nAchRs.  The modelling contributions in this paper included producing homology models for extracellular domains of the receptor subtypes (see image below), docking the cytisine derivative compounds into each of these and performing molecular dynamics simulations using GROMACS.  Careful examination of the compound behaviour and binding interactions within the different receptor subtypes allowed a rationalisation for the observed in vitro binding affinities.