Embedded within the complexity of biological systems lies a formidable task: deciphering the intricate architecture of macromolecules. In this Viewpoint, a panel of experts discuss the key challenges and opportunities of macromolecular structure determination, highlighting the crucial synergy between empirical experimentation and artificial intelligence-based techniques in unravelling these complexities.
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The contributors
Xiaochen Bai Xiaochen Bai is an associate professor at UT Southwestern Medical Center. He has been working on cryo-EM method development and structural determination for more than a decade. His lab currently focuses on the structural and functional studies of receptor tyrosine kinases.
Tamir Gonen Tamir Gonen is a membrane biophysicist and an expert in crystallography and cryo-EM. He is a professor of biological chemistry and physiology at the David Geffen School of Medicine at UCLA and an investigator of the Howard Hughes Medical Institute and a member of the Royal Society of New Zealand. His group develops methodologies for studying medically important membrane protein structure and dynamics.
Angela Gronenborn Angela M. Gronenborn is a structural biologist who has developed and applied NMR methods since 1980. She had led research groups at NIMR in London, at the Max Planck Institute in Martinsried, the intramural research programme of NIDDK, NIH, and finally at the School of Medicine of the University of Pittsburgh from 2005 to the present. She also serves as director of the Pittsburgh Center for HIV Protein Interactions.
Anastassis Perrakis Anastassis (Tassos) Perrakis was trained as an X-ray crystallographer and biochemist at the EMBL. Throughout his career, he provides structural understanding into key questions about the relationship of structure and function in cell biology and biochemistry, and develops software and resources for deciphering and understanding protein structure and function.
Andrea Thorn Andrea Thorn works both experimentally, solving molecular structures from viruses and fungi by crystallography and cryo-EM, and computationally, developing methods for experimental data in structural biology. She started and led the international Coronavirus Structural Task Force and her group develops AI-based tools for diffraction diagnostics (AUSPEX) and for reconstruction map annotation (HARUSPEX).
Jianyi Yang Jianyi Yang is a distinguished professor of mathematics and interdisciplinary sciences at Shandong University. He has made notable contributions to the field of protein structure and function prediction through his co-development of several widely used algorithms, including trRosetta, I-TASSER, COACH and BioLiP. His research group, known as Yang-Server, ranked at the top in the prediction of protein tertiary structure in the CASP15 experiment.
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Bai, Xc., Gonen, T., Gronenborn, A.M. et al. Challenges and opportunities in macromolecular structure determination. Nat Rev Mol Cell Biol 25, 7–12 (2024). https://doi.org/10.1038/s41580-023-00659-y
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DOI: https://doi.org/10.1038/s41580-023-00659-y
