Professor Wayne A. Hendrickson from Columbia University was invited by IBP to give a report entitled AlphaFold in Analyzing Protein Crystal Structures on Nov 14, 2023. The lecture was presided by Professor Fei Sun. The Principal Investigators and students from IBP attended the report.

Professor Hendrickson is a fellow of the American Academy of Arts and Sciences and a member of the National Academy of Sciences. His honors include the Aminoff Prize of the Royal Swedish Academy of Sciences, the Gairdner International Award, the Harvey Prize of the Technion - Israel Institute of Technology, and the Ewald Prize of the International Union of Crystallography. He proposed and established the Multi-wavelength Anomalous Dispersion (MAD) method, which has been widely used and provided a strong technical support for the development of structural biology. His research team also solved many important protein structures, such as CD4, CD8, insulin receptor kinase, Hsp70, SRC kinase, HIV gp120, calmodulin, FGF, etc., providing important information for understanding the molecular mechanisms of human diseases and drug development.

In the report, Professor Hendrickson first introduced the background of protein crystallography, and explained several methods for determining crystal phases in analyzing protein crystal structures, including Multiple Isomorphous Replacement (MIR), Single Isomorphous Replacement (SIR), Single-wavelength Anomalous Diffraction (SAD), etc., as well as the principles and applications of density modification for crystal structures. Then, Professor Hendrickson showed the basic principles, technical features and development trends of the structure prediction algorithm AlphaFold, explained the impact of AlphaFold on protein crystallography, and demonstrated several methods to analyze protein crystal structures with the help of AlphaFold. Professor Hendrickson proved that AlphaFold can effectively assist molecular replacement (AlphaFold-guided MR), and developed a software to automate the calculation of this process. For low-resolution crystal structures, Professor Hendrickson proposed a Quasi-rigid-body AlphaFold/Rosetta-assisted Low-resolution Structure (QARLS Refinement) method based on AlphaFold and Rosetta software, which can build and correct more accurate crystal structures, and showed the effectiveness of this method in the examples of RyR1 and other protein crystal structures.

Finally, Professor Hendrickson summarized and prospected the impact of AlphaFold on structural biology. He believes that AlphaFold is very successful in predicting protein structures, and its training data mainly comes from a large number of protein crystal structures already solved in the PDB database, and most of the crystal structures are based on the MAD and SAD methods. We could use the AlphaFold-assisted molecular replacement method to determine new crystal structures, and use the "QARLS" method to assist in the correction of low-resolution crystal structures. In addition, AlphaFold also promotes the development of cryo-electron microscopy structure research technology to some extent. However, despite AlphaFold's remarkable achievements in predicting protein structures, Professor Hendrickson believes that experimental data is still essential for understanding new protein structures.

After the report, Professor Hendrickson had a lively discussion and exchange with the audience, and answered various questions they raised. The report was a complete success, providing a valuable learning and exchange opportunity for the professors and students who attended the meeting.

Professor Wayne A. Hendrickson was giving the lecture

Professor Fei Sun hosted the lecture

Prof. Fei Sun and Prof. Wayne A. Hendrickson

The audience