title: Serial femtosecond crystallography: A revolution in structural biology.
abstract: Macromolecular crystallography at synchrotron sources has proven to be the most influential method within structural biology, producing thousands of structures since its inception. While its utility has been instrumental in progressing our knowledge of structures of molecules, it suffers from limitations such as the need for large, well-diffracting crystals, and radiation damage that can hamper native structural determination. The recent advent of X-ray free electron lasers (XFELs) and their implementation in the emerging field of serial femtosecond crystallography (SFX) has given rise to a remarkable expansion upon existing crystallographic constraints, allowing structural biologists access to previously restricted scientific territory. SFX relies on exceptionally brilliant, micro-focused X-ray pulses, which are femtoseconds in duration, to probe nano/micrometer sized crystals in a serial fashion. This results in data sets comprised of individual snapshots, each capturing Bragg diffraction of single crystals in random orientations prior to their subsequent destruction. Thus structural elucidation while avoiding radiation damage, even at room temperature, can now be achieved. This emerging field has cultivated new methods for nanocrystallogenesis, sample delivery, and data processing. Opportunities and challenges within SFX are reviewed herein.
authors.affiliation: School of Molecular Sciences, Arizona State University, Tempe, AZ 85287-1604, USA; Center for Applied Structural Discovery, The Biodesign Institute, Arizona State University, Tempe, AZ 85287-7401, USA.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Martin-Garcia
authors.affiliation: School of Molecular Sciences, Arizona State University, Tempe, AZ 85287-1604, USA; Center for Applied Structural Discovery, The Biodesign Institute, Arizona State University, Tempe, AZ 85287-7401, USA.
authors.forename: Chelsie E
authors.initials: CE
authors.lastname: Conrad
authors.affiliation: School of Molecular Sciences, Arizona State University, Tempe, AZ 85287-1604, USA; Center for Applied Structural Discovery, The Biodesign Institute, Arizona State University, Tempe, AZ 85287-7401, USA.
authors.forename: Jesse
authors.initials: J
authors.lastname: Coe
authors.affiliation: School of Molecular Sciences, Arizona State University, Tempe, AZ 85287-1604, USA; Center for Applied Structural Discovery, The Biodesign Institute, Arizona State University, Tempe, AZ 85287-7401, USA.
authors.forename: Shatabdi
authors.initials: S
authors.lastname: Roy-Chowdhury
authors.affiliation: School of Molecular Sciences, Arizona State University, Tempe, AZ 85287-1604, USA; Center for Applied Structural Discovery, The Biodesign Institute, Arizona State University, Tempe, AZ 85287-7401, USA. Electronic address: pfromme@asu.edu.
authors.forename: Petra
authors.initials: P
authors.lastname: Fromme
mesh_terms: D003198:Computer Simulation; D003460:Crystallization / Q000379:methods* / Q000639:trends; D008958:Models, Molecular; D011487:Protein Conformation; D011506:Proteins / Q000138:chemical synthesis* / Q000648:ultrastructure*; D014961:X-Ray Diffraction / Q000379:methods* / Q000639:trends
chemical_list: D011506:Proteins
keywords: Membrane proteins; Nanocrystals; Protein crystallography; Serial femtosecond crystallography; X-ray free electron lasers