MS12-05 - ALEPH: A New Software for Structural Analysis and Generation of Fragment Libraries for Molecular Replacement

Ana Medina (Institute of Molecular Biology of Barcelona, Spanish National Research Council (IBMB-CSIC), Spain)

"ARCIMBOLDO1 is a fragment based molecular replacement framework where Local Folds (LF: small discontinuous fragments) are located with PHASER2 providing phases that are improved and interpreted in SHELXE3. ALEPH4 is a program for retrieving structural properties of proteins from the PDB5, based solely on geometrical descriptors, Characteristic Vectors (CVs)6, computed as centroid Cα-O vectors on consecutive tripeptides. Networks of CVs hold angles and distances representing protein structure. ALEPH implements four different tasks: Annotation: a customizable secondary and tertiary structure analysis to map general or local properties controlling the strictness of the annotation. Decomposition: structure subdivision into smaller compact folds. ARCIMBOLDO_SHREDDER1 gives the model internal degrees of freedom based on this decomposition. Library generation: to extract and cluster fragment libraries collecting structural variations of the same fold. Each library expresses a common pattern as the hypothesis for phasing whereas ARCIMBOLDO_BORGES1 jointly evaluates results for all models, revealing correct solutions. Superposition: align a fragment onto a complete structure. A graphical user interface is provided to perform each task and to visualize and plot the results in real time. 

[1] Millán, C. et al., (2015) IUCrJ., 1, 95. 
[2] McCoy, AJ, et al. (2007). J Appl Crystallogr 40, 658. 
[3] Usón, I & Sheldrick, G. (2018) Acta Cryst. D74, 106. 
[4] Medina, A., et al. (2019) In preparation. 
[5] Berman, H., et al.(2015) Nucleic Acids Research. 35, D301 
[6] Sammito, M., et al. (2013). Nat Methods. 10, 1099."