Newcomers to the field of structural biology, which aims to understand life at the molecular level, see a vast number of existing results and are faced with a diverse range of experimental methods. These are used singly or in various combinations, however the uncertainties of the results found are unfortunately not fully assessed.Beginning with the basic physics of describing systematic and random errors, this book aims to explore these uncertainties, by examining the accuracy of each experimental method used to determine a 3D biological macromolecule structure and its dynamics, and their various possible combinations. The book also discusses the uncertainties in our determination of atomic positions in our static structures, and our analysis of the living cell. Aimed at graduate students from a wide range of science disciplines including physics, chemistry, biology, and mathematics, this book provides an overview of the topic of precision and accuracy in biological crystallography, diffraction, scattering, microscopies, and spectroscopies.
Preface; Acknowledgements; About the author; Introduction; The physics of errors as illustrated by X-ray crystallography; History of the reliability of structure determination methods; Mass spectrometry; Structure validation approaches; Other validation tools: Round-robin projects; Similarities and differences in the probes used in structure determination; Fibre diffraction; Powder diffraction; Small-angle solution scattering; Electron microscopy (EM); X-ray absorption spectroscopy (XAS); NMR; EPR for metalloproteins; Combining methods for accuracy; Combining methods to span different length scales; Role of simulations of structural dynamics as a complement to experimental studies; Role of predictions as a grand challenge in biology: Protein fold prediction is solved; A new method: X-ray photon correlation spectroscopy (XPCS) to study biocondensed matter; Conclusions; Appendix A1: Bayesian reasoning in data analysis and model refinement; Bibliography; Abbreviations List; Index;
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