2017 ACA Workshops

 

 

Cryo-­‐EM -A Guide to High‐Resolution Structure Determination         

 

Organizers:

 

Wah Chiu

 

Lori Passmore

 

John Rubinstein

Stanford University

 

MRC LMB, Cambridge UK

 

Sick Kids, Toronto

 

[email protected]

 

[email protected]

 

[email protected]

Description:

 

Over the past five years, cryo-EM has become increasingly popular and is now the method of choice for structure determination of proteins larger than ~200 kDa. It has been particularly successful for proteins that are difficult to crystallize, including membrane proteins, large assemblies and multi-protein complexes. The aim of this workshop is to provide a detailed overview of cryo-EM specimen preparation, image processing and building/refinement of atomic models. The workshop will focus on high-resolution single particle cryo-EM. Aspects of image processing and modelling will be hands-on - state-the-art programs will be used by the students to process sample datasets.

 

User facilities are being established in many universities and these will allow a larger community to access cryo-EM. By teaching the main concepts and challenges in each step, this workshop will benefit those who want to use cryo-EM in the future, or who have recently transitioned into it. The organizers are experts in the topics they will be teaching and all have been involved in methods development. We will strive to include up-to-date discussions of cutting-edge methods and technology.

 

 

 

Molecular Art & Animation in 3D                                                             

 

Organizers:

 

Chelsy C Chesterman

Rutgers, University

[email protected]

 

Description:

 

Beautiful figures and animations have become synonymous with the publication of structural data in top research journals. Demonstrating molecular concepts and structural data using these strategies is also highly effective in scientific presentations or outreach activities. Many crystallographers enter the field with a background in biology or chemistry and are unfamiliar with creating such artwork. This workshop will focus on the creation of figures and animations in multiple software programs including PyMOL, Chimera, Blender 3D, and Maya. Topics will include factors to consider when designing your art and animations, basic operation of these programs, and follow-along examples. The main goal of the workshop will be to give participants an overview of the available tools so that they can start to explore creating their own molecular art.

 

 

 

Applications of Small Angle Scattering to Structural Biology: An Introduction                                                                            

 

Organizers:

 

Kushol Gupta

Perelman School of Medicine

University of Pennsylvania

 

[email protected]

Richard Gillilan

Macromolecular Diffraction Facility

Cornell High Energy Synchrotron Source

 

[email protected]

Jesse Hopkins

Macromolecular Diffraction Facility

Cornell High Energy Synchrotron Source

 

[email protected]

Haydyn Mertens

BIOSAXS Group

EMBL Hamburg

 

[email protected]

Srinivas Chakravarthy

BioCAT Group

Advanced Photon Source

[email protected]

 

Description:

 

Small angle X-ray and neutron scattering (SAXS/SANS, or SAS) has experienced dramatic growth over the past fifteen years within the structural biology community, emerging as an important and versatile analytical technique for the study of the structure and function of biological macromolecules in solution. Publications that employ the technique on biological macromolecules appear in Pubmed at a rate of ~one per day. Based on this and recent successful workshops at the 2013, 2015, and 2016 ACA meetings, we believe the 2018 meeting in Toronto will serve as an excellent destination for bringing together SAS experts to prepare students and investigators new to the method for the successful application of this technique. We propose a one-day workshop providing introduction to both the theory of the method and best practices common to the field. In addition to synchrotron sources, this workshop will devote content to laboratory x-ray sources and contrast variation using neutron sources.

 

 

 

Rietveld Refinement And Pair Distribution Function Analyses Of In Situ X-Ray Scattering Data Within GSAS-‐II                                                          

 

Organizers:

 

Olaf J. Borkiewicz

Argonne National Laboratory

[email protected]

 

Description:

 

This workshop will be a foray into structural analysis of powder X-¬‐ray scattering data - one of the most comprehensive and powerful tools for evaluating crystal structures. The primary goal of this workshop will be to discuss and explain all typical steps involved in structural analysis of X-¬‐ray scattering data with emphasis on data collected at modern users' facilities using large-¬‐area detectors. These will include such aspects of the experiment as measurement calibration, data reduction, peak profile fitting, Rietveld refinement and others.  In addition to "classic" single pattern refinement approach, we will explore strategies for handling large data sets, i.e. sequential refinements and parametric fitting to in situ and operando data. Part of the workshop will be also dedicated to the complementary use of pair distribution function (PDF) analysis, which allow extraction of structural information from amorphous and disordered materials, for which classical crystallographic approaches may not yield satisfactory results.  All tasks pertaining to the workshop will be accomplished within General Structure Analysis System (GSAS-¬‐II). GSAS-¬‐ II is a powerful open-¬‐source Python-based tool that addresses all types of crystallographic studies and handles all standard activities involved in the reduction and analysis of data acquired with both X-ray and neutron probes. This will be an excellent opportunity to learn how to take full advantage of this powerful software directly from the program authors, Robert Von Dreele and Brian Toby, and how to apply this knowledge to real-world applications and experimental data sets presented by beamline scientists, Kamila Wiaderek, Andrey Yakovenko and Olaf Borkiewicz, Advanced Photon Source, Argonne   National Laboratory.

 

 

 

X-­‐Ray Crystallography: Structure Preparation, Electron Density & Solvent Analysis                                                 

 

Organizers:

 

Raul Alvarez

Chemical Computing Group

[email protected]

 

Description:

 

Drug discovery and design studies in the pharmaceutical and biotech industries and in academia are usually based, directly or indirectly, on crystallographic information from publicly available databases such as the PDB, from in-house proprietary structures, or from both. It is therefore useful for crystallographers working in biomolecular systems, particularly those early in their careers, to understand how the information that they produce is leveraged.

 

This hands-on workshop will cover methods for evaluating, analyzing and refining protein models derived from X-ray crystallographic data. These will include the modeling of loops whose placement could not be determined from electron density data, assignment of sidechain positions through the assessment of rotamers, and determination of protonation and tautomeric states, all of which are embodied in the Structure Preparation application in MOE (Molecular Operating Environment), the software system to be used at this workshop.

 

Analyses of protein geometry will be performed, through calculation of Ramachandran and other plots, allowing targeted optimization of the structural model. Visualization of temperature factors, plotting of electron density maps, and an analysis of protein-ligand interactions will all be described. Crystal contacts, often overlooked in biomolecular structures, will also be displayed and examined.

 

The 3D-RISM method for predicting and refining the placement of solvent molecules in protein and protein-ligand structural models will be presented, with a discussion about the role of water displacement in ligand binding.

 

Attendees will therefore gain an appreciation as to how crystallographic structural information feeds into the drug discovery and design process, emphasizing interpretation and communication, with the aim of smoothing the interface between the "suppliers" and "consumers" of biomolecular structural data.