BrisSynBio:a BBSRC/EPSRC-funded Synthetic Biology Research Centre

BrisSynBio is the Bristol-based Biotechnology and Biological Sciences Research Council (BBSRC)/Engineering and Physical Sciences Research Council (EPSRC)-funded Synthetic Biology Research Centre. It is one of six such Centres in the U.K. BrisSynBio's emphasis is on rational and predictive bimolecular modelling, design and engineering in the context of synthetic biology. It trains the next generation of synthetic biologists in these approaches, to facilitate translation of fundamental synthetic biology research to industry and the clinic, and to do this within an innovative and responsible research framework

Assessing cellular response to functionalized α-helical peptide hydrogels

α-Helical peptide hydrogels are decorated with a cell-binding peptide motif (RGDS), which is shown to promote adhesion, proliferation, and differentiation of PC12 cells. Gel structure and integrity are maintained after functionalization. This opens possibilities for the bottom-up design and engineering of complex functional scaffolds for 2D and 3D cell cultures.</p

CCBuilder:An interactive web-based tool for building, designing and assessing coiled-coil protein assemblies

Motivation: The ability to accurately model protein structures at the atomistic level underpins efforts to understand protein folding, to engineer natural proteins predictably and to design proteins de novo . Homology-based methods are well established and produce impressive results. However, these are limited to structures presented by and resolved for natural proteins. Addressing this problem more widely and deriving truly ab initio models requires mathematical descriptions for protein folds; the means to decorate these with natural, engineered or de novo sequences; and methods to score the resulting models. Results: We present CCBuilder, a web-based application that tackles the problem for a defined but large class of protein structure, the α-helical coiled coils. CCBuilder generates coiled-coil backbones, builds side chains onto these frameworks and provides a range of metrics to measure the quality of the models. Its straightforward graphical user interface provides broad functionality that allows users to build and assess models, in which helix geometry, coiled-coil architecture and topology and protein sequence can be varied rapidly. We demonstrate the utility of CCBuilder by assembling models for 653 coiled-coil structures from the PDB, which cover &gt;96% of the known coiled-coil types, and by generating models for rarer and de novo coiled-coil structures. Availability and implementation: CCBuilder is freely available, without registration, at http://coiledcoils.chm.bris.ac.uk/app/cc_builder

Ag on Ge(111): 2D X-ray structure analysis of the (Wurzel)3 x (Wurzel)3 superstructure

We have studied the Ag/Ge(111)(Wurzel)3 x (Wurzel)3 superstructure by grazing-incidence X-ray diffraction. In our structural analysis we find striking similarities to the geometry of Au on Si(111). The Ag atoms form trimer clusters with an Ag-Ag distance of 2.94+-0.04°A with the centers of the trimers being located at the origins of the (Wurzel)3 x (Wurzel)3 lattice. The Ag layer is incomplete and at least one substrate layer is distorted

Applying graph theory to protein structures:An atlas of coiled coils

Motivation: To understand protein structure, folding and function fully and to design proteins de novo reliably, we must learn from natural protein structures that have been characterised experimentally. The number of protein structures available is large and growing exponentially, which makes this task challenging. Indeed, computational resources are becoming increasingly important for classifying and analysing this resource. Here, we use tools from graph theory to define an atlas classification scheme for automatically categorising certain protein substructures. Results: Focusing on the α-helical coiled coils, which are ubiquitous protein-structure and protein-protein interaction motifs, we present a suite of computational resources designed for analysing these assemblies. iSOCKET enables interactive analysis of side-chain packing within proteins to identify coiled coils automatically and with considerable user control. Applying a graph theory-based atlas classification scheme to structures identified by iSOCKET gives the Atlas of Coiled Coils, a fully automated, updated overview of extant coiled coils. The utility of this approach is illustrated with the first formal classification of an emerging subclass of coiled coils called α-helical barrels. Furthermore, in the Atlas, the known coiled-coil universe is presented alongside a partial enumeration of the ‘dark matter’ of coiled-coil structures; i.e., those coiled-coil architectures that are theoretically possible but have not been observed to date, and thus present defined targets for protein design. Availability: iSOCKET is available as part of the open-source GitHub repository associated with this work (https://github.com/woolfson-group/isocket). This repository also contains all the data generated when classifying the protein graphs. The Atlas of Coiled Coils is available at: http://coiledcoils.chm.bris.ac.uk/atlas/app

Interpretation of heart rate variability via detrended fluctuation analysis and alpha-beta filter

Detrended fluctuation analysis (DFA), suitable for the analysis of nonstationary time series, has confirmed the existence of persistent long-range correlations in healthy heart rate variability data. In this paper, we present the incorporation of the alpha-beta filter to DFA to determine patterns in the power-law behaviour that can be found in these correlations. Well-known simulated scenarios and real data involving normal and pathological circumstances were used to evaluate this process. The results presented here suggest the existence of evolving patterns, not always following a uniform power-law behaviour, that cannot be described by scaling exponents estimated using a linear procedure over two predefined ranges. Instead, the power law is observed to have a continuous variation with segment length. We also show that the study of these patterns, avoiding initial assumptions about the nature of the data, may confer advantages to DFA by revealing more clearly abnormal physiological conditions detected in congestive heart failure patients related to the existence of dominant characteristic scales.Comment: 18 pages, 14 figure

Spectral Simplicity of Apparent Complexity, Part I: The Nondiagonalizable Metadynamics of Prediction

Virtually all questions that one can ask about the behavioral and structural complexity of a stochastic process reduce to a linear algebraic framing of a time evolution governed by an appropriate hidden-Markov process generator. Each type of question---correlation, predictability, predictive cost, observer synchronization, and the like---induces a distinct generator class. Answers are then functions of the class-appropriate transition dynamic. Unfortunately, these dynamics are generically nonnormal, nondiagonalizable, singular, and so on. Tractably analyzing these dynamics relies on adapting the recently introduced meromorphic functional calculus, which specifies the spectral decomposition of functions of nondiagonalizable linear operators, even when the function poles and zeros coincide with the operator's spectrum. Along the way, we establish special properties of the projection operators that demonstrate how they capture the organization of subprocesses within a complex system. Circumventing the spurious infinities of alternative calculi, this leads in the sequel, Part II, to the first closed-form expressions for complexity measures, couched either in terms of the Drazin inverse (negative-one power of a singular operator) or the eigenvalues and projection operators of the appropriate transition dynamic.Comment: 24 pages, 3 figures, 4 tables; current version always at http://csc.ucdavis.edu/~cmg/compmech/pubs/sdscpt1.ht