National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM128867
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
P41GM136508
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM136614
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM007185
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
AI143368
米国
Sao Paulo Research Foundation (FAPESP)
16/24191-8
米国
Sao Paulo Research Foundation (FAPESP)
17/13485-3
ブラジル
Spanish Ministry of Science, Innovation, and Universities
BES-2015-071397
米国
Spanish Ministry of Economy and Competitiveness
PGC2018-101370-B-100,
スペイン
Spanish Ministry of Economy and Competitiveness
MDM2014-0435-01
スペイン
Other government
2017SGR- 1192
スペイン
引用
ジャーナル: ACS Bio Med Chem Au / 年: 2023 タイトル: Fragment-Based Phasing of Peptidic Nanocrystals by MicroED. 著者: Logan S Richards / Maria D Flores / Claudia Millán / Calina Glynn / Chih-Te Zee / Michael R Sawaya / Marcus Gallagher-Jones / Rafael J Borges / Isabel Usón / Jose A Rodriguez / 要旨: Electron diffraction (MicroED/3DED) can render the three-dimensional atomic structures of molecules from previously unamenable samples. The approach has been particularly transformative for peptidic ...Electron diffraction (MicroED/3DED) can render the three-dimensional atomic structures of molecules from previously unamenable samples. The approach has been particularly transformative for peptidic structures, where MicroED has revealed novel structures of naturally occurring peptides, synthetic protein fragments, and peptide-based natural products. Despite its transformative potential, MicroED is beholden to the crystallographic phase problem, which challenges its determination of structures. ARCIMBOLDO, an automated, fragment-based approach to structure determination, eliminates the need for atomic resolution, instead enforcing stereochemical constraints through libraries of small model fragments, and discerning congruent motifs in solution space to ensure validation. This approach expands the reach of MicroED to presently inaccessible peptide structures including fragments of human amyloids, and yeast and mammalian prions. For electron diffraction, fragment-based phasing portends a more general phasing solution with limited model bias for a wider set of chemical structures.