Emergent organisation in complex biomolecular systems

Complexity and self-organisation are critical yet poorly understood phenomena. This project aims to develop and apply mathematical and computational approaches that will identify principles governing the emergent organisation of selforganising biomolecular systems. Computational methods for characterising the dynamics of these intrinsically complex processes will be developed and applied to protein folding and molecular self-assembly. The methodologies will focus on the complexity of the system’s dynamics thus advancing fundamental knowledge concerning the role of complexity in biological systems. A composite approach will be pursued, focusing on critical aspects of the problems defining the route from sequence (chemical formula) to complex functionality of native structures. This involves determination of the underlying potential energy and fitness surfaces together with their topological, statistical and dynamic properties for models of polypeptides and RNA self-organization; finding the features of the energy funnel for simplified protein in water models in order to distinguish between and understand “good” and “bad” folders; characterising biomolecular dynamics in terms of information flows between different timeand length-scales (for which the aggregation of spatial information can be used to detect emergent structures); reconstructing dynamic hierarchies in model biopolymer systems thus directly detecting the emergence of the dynamic forms and information flow on different spatiotemporal scales in the system; and calculating the statistical complexity of model biomolecular systems and the key parts of realistic biomolecules. The data for these investigations will be obtained from sophisticated all-atom simulations of realistic biomolecular systems and experimental mechanical stretching of giant single molecular proteins. The improved understanding that will be obtained of the dynamical complexity of native and folding biomolecular systems should provide a basis for the accurate calculation of biomolecular folding and function and will therefore be of fundamental relevance to biology, medicine and biotechnology. 1. Project objective(s)