Computational Molecular Biophysics

Principal Investigator: Dr. Josh BERRYMAN


Our bodies are home to a variety of molecular machines, single molecules from tens of atoms (e.g. a peptide hormone) up to billions of atoms (e.g. a chromosome).   These machines are soft and flexible, often acting with some element of randomness, but they obey the same laws of physics that apply to everything else.  The work of our group is to construct in-silico models of molecular systems in order to analyse and predict their behaviour.  Our particular studies are the mechanics and interactions of peptides and DNA.

The assembly of peptides into mesoscopic aggregates is very relevant to diseases, particularly to the amyloid family of neurodegenerative diseases, however this process is very versatile and can result in materials with a wide range of positive properties, even starting from the same ingredients.  Peptides can assemble to make biocompatible fibres as strong as silk, as well as membranes, micelles and antimicrobial gels.

The mechanical properties of DNA are related to its function in the cell. DNA is stretched, twisted, folded, unzipped and generally manipulated in the course of storing and sharing genetic information. The details of these processes are very hard to observe directly, hence computer models are of particular use to understand this charismatic molecule in action.

(1) DNA can make radical changes of structure under twist stress (B to Z) and extensional stress (B to Σ).

(2) Small peptides can assemble to make a variety of structures with a wide range of properties. The outcome of the assembly process is delicately balanced and hard to predict.

Connections to other local activities:

– Tkatchenko: understanding molecular interactions is the basis of effective in silico modelling.

– Esposito: Esposito’s methods are amenable to describing some of the processes which we attempt to quantify, from a new perspective of nonequilibrium thermodynamics.

– Balling, Grünewald, Mittelbronn: the LCSB (director Rudi Balling) has a significant investment in understanding neurodegenerative diseases from a systems perspective, including work in the groups of Grunewald, Mittelbronn and others.  Peptide assembly is a molecular mechanism which can be understood in an atomistic way, giving a reductionist approach to these diseases which is complementary to the holistic approach of the LCSB.

– Brida: Raman and Infrared spectroscopy are valuable experimental tools to complement molecular simulations as the dynamics probed by these techniques are also accessible in silico, allowing comparison of simulation (explicit but often uncertain) with experiment, where information is reliable but often incomplete.

– Sengupta: Bacterial films and mats are often composed of peptide nanomaterials.

Connections to other international activities:

International collaborations to develop molecular simulation tools:

The Amber Home Page

Extensible Simulation Package for Research on Soft Matter