Ebook: Advancing Methods for Biomolecular Crystallography

This work presents a snapshot of the state of the art of modern biomolecular crystallography, from crystallisation through structure determination and even interactive presentation on the web. Methods driving the latest automated structure determination pipelines are explained, as well as how to deal with problems such as crystal pathologies that still demand expert analysis. These methods are illustrated through their application to problems of great biological interest, such as the molecular machinery underlying the complement pathway, the mechanism of action of monoamine oxidase inhibitors, and the structure of the eukaryotic ribosome. Complementary approaches, such as neutron diffraction, small angle X-ray scattering, coherent diffraction and computational modelling, are also explored.

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This work presents a snapshot of the state of the art of modern biomolecular crystallography, from crystallisation through structure determination and even interactive presentation on the web. Methods driving the latest automated structure determination pipelines are explained, as well as how to deal with problems such as crystal pathologies that still demand expert analysis. These methods are illustrated through their application to problems of great biological interest, such as the molecular machinery underlying the complement pathway, the mechanism of action of monoamine oxidase inhibitors, and the structure of the eukaryotic ribosome. Complementary approaches, such as neutron diffraction, small angle X-ray scattering, coherent diffraction and computational modelling, are also explored.

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This work presents a snapshot of the state of the art of modern biomolecular crystallography, from crystallisation through structure determination and even interactive presentation on the web. Methods driving the latest automated structure determination pipelines are explained, as well as how to deal with problems such as crystal pathologies that still demand expert analysis. These methods are illustrated through their application to problems of great biological interest, such as the molecular machinery underlying the complement pathway, the mechanism of action of monoamine oxidase inhibitors, and the structure of the eukaryotic ribosome. Complementary approaches, such as neutron diffraction, small angle X-ray scattering, coherent diffraction and computational modelling, are also explored.

Content:
Front Matter....Pages i-xiii
The Zen of Model Anomalies – Correct Most of Them. Treasure the Meaningful Valid Few. Live Serenely with the Rest!....Pages 1-10
Total Chemical Protein Synthesis for the Determination of Novel X-ray Structures by Racemic Protein Crystallography....Pages 11-22
Crystal Pathologies....Pages 23-31
Crystallizing Membrane Proteins for Structure-Function Studies Using Lipidic Mesophases....Pages 33-46
Searching for Needles in Haystacks: Automation and the Task of Crystal Structure Determination....Pages 47-57
Data Processing: How Good Are My Data Really?....Pages 59-68
Radiation Damage in Macromolecular Crystallography: What Is It and Why Do We Care?....Pages 69-77
Elemental Analysis of Proteins by Proton Induced X-ray Emission (microPIXE)....Pages 79-89
X-rays-Induced Cooperative Atomic Movement in a Protein Crystal....Pages 91-103
Everything Happens at Once – Deconvolving Systematic Effects in X-ray Data Processing....Pages 105-112
Extending the Reach of Molecular Replacement....Pages 113-122
Phasing Through Location of Small Fragments and Density Modification with ARCIMBOLDO....Pages 123-133
SAD/MAD Phasing....Pages 135-149
Macromolecular Phasing: Solving the Substructure....Pages 151-157
Advanced Applications of Shelxd and Shelxe....Pages 159-167
Use of a Weak Anomalous Signal for Phasing in Protein Crystallography: Reflection from Personal Experience....Pages 169-180
Model-Building and Reduction of Model Bias in Electron Density Maps....Pages 181-192
Using Coot to Model Protein and Ligand Structures Using X-ray data....Pages 193-203
Crystallographic Structure Refinement in a Nutshell....Pages 205-209
Crystallographic Maps and Models at Low and at Subatomic Resolutions....Pages 211-219
High Resolution Macromolecular Crystallography....Pages 221-230
Publishing in Proteopedia: The Guide....Pages 231-258
Proteolysis, Complex Formation and Conformational Changes Drive the Complement Pathways....Pages 259-275
Monoamine Oxidase Inhibitors: Diverse and Surprising Chemistry with Expanding Pharmacological Potential....Pages 277-295
Structure of the Eukaryotic Ribosome: Tips and Tricks....Pages 297-307
Neutron Protein Crystallography. How to Proceed the Experiments to Obtain the Structural Information of Hydrogen, Protons and Hydration in Bio-macromolecules....Pages 309-312
Coherent Diffraction and Holographic Imaging of Individual Biomolecules Using Low-Energy Electrons....Pages 313-320
Structure Analysis of Biological Macromolecules by Small-Angle X-ray Scattering....Pages 321-330
Protein Structure Modeling with Rosetta: Case Studies in Structure Prediction and Enzyme Repurposing....Pages 331-342
....Pages 343-351