Humans to proteins

Computational studies in life sciences not only provide a new way of complementing experimental studies, they offer a practical means of bringing new solutions and understanding in diagnostic and curative medicine, medical technology, drug design and pharmacology, agrochemicals, agriculture and food production. The fruits of this computational research are humane, benevolent and highly lucrative at the same time! This volume specialises in selected examples of computational applications covering such diverse, yet complementary, areas of medicine and anatomy, neurophysiology as well as biochemistry, molecular biology and bioinformatics, and their subsequent impact on cognitive philosophy. Computational medicine is represented by reports on "Visual Human: Male and Female"—the most detailed and comprehensive collection of human anatomical data (MRI, CAT and visual) ever recorded—and on computer-aided diagnosis from medical X-ray images using anatomical models. Computational neurophysiology topics cover EEG simulation of the cortex, large scale simulation of multi-layer and patchy cortex-like systems, simulation of large scale, anatomically realistic networks of intestinal (enteric) neurons during reflexes, and modelling of long-term synaptic potentiation and depression. A chapter on computers and computations in cognitive science explodes the domain of discussed topics from physiology to philosophy: are cognitive systems computers or dynamical systems? The remaining seven chapters deal with various aspects of molecular biology, protein biochemistry and bioinformatics. Molecular dynamics is applied to study protein dynamics. The results are compared with structural and dynamic X-ray diffraction and NMR spectroscopy data and may help elucidate the degree of overlap between these two techniques, as well as help to predict quantities not determined experimentally. Results of atomic resolution molecular dynamics simulations of gramicidin A channels in a phospholipid membrane and comparison with solid state NMR are reviewed. Reaction mechanisms in enzyme active sites are studied using a "divide and conquer" approach of hybrid quantum and molecular mechanics. Other chapters deal with protein structure prediction and the challenge of genome projects; the prediction of binding peptides utilising experimental binding data and reported binding motifs combined with genetic algorithms and artificial neural networks; application of interactive computer graphics in analysis of molecular sequences and general issues of successful delivery of computational resources to the users—the biologists. The phenomena covered in this volume span many length-scales: from the human scale (whole organism, anatomy) through to organs (cortex, large networks of neurons, enteric nervous system) to macromolecular (proteins, enzymes, phospholipid membranes); from -T m, through --10-2 m to ~10-10 m. The time-scales relevant to the topics in the book span 24 orders of magnitude: from tens of years ~109 s, anatomical models of human ageing) to femtoseconds (10-15 s, time-step in molecular dynamics simulations). The most obvious prospective benefits of the work reported include: (a) studies of deformation of the human form to simulate obesity, muscle building, infection and trauma—both acute and long term development and deterioration of the human form; (b) remote surgical operations with haptic feedback; (c) reduced risk of missed diagnoses, particularly in screening applications; (d) understanding of how dynamic patterns of brain activity may be related to underlying neurophysiological processes and structures; (e) understanding of protein-lipid interactions at the molecular level, delivery of drugs, permeation through membranes; (f) understanding of possible links of the motional properties of the protein to its biological function; (g) organisation and systematisation of DNA sequences and genome data, elucidation of protein structure-function relationship; (h) understanding of the effects of mutations in genetic disease. The wide coverage of topics presented here constitute a strong argument for the celebrated "Unity of Science". We see how a fundamental physical description, common mathematical formalism, computing methods, modelling and simulation techniques, and computer visualisation help advance our knowledge of living form—all through the use of powerful computers. We witness how traditionally diverse fields of life science merge and the most promising challenges await across topical divisions. The editor would like to thank his co-workers and friends for their help, support and guidance in organising the Melbourne Symposium (John O"Callaghan, Sue Wilson, Rob Bell, Heather Vile, Virginia Norling, Len Makin, Jim Taylor, Andrzej Mielczarek and Anna Maciejewska) and in producing this book (Kevin Jeans, Kylie Crane, Trevor Clarke, Alexa Cloud-Guest and Linda Kemp). Special thanks to Aleksa Michalewicz and Lura Downie for corrections work for this volume. It has been a challenging, rewarding and, at times, trying experience—thank you for all your respective contributions. Marek Michalewic