MS09-04 - ARCIMBOLDO Towards Low Resolution: Recent Updates

Rafael Borges (Institut de Biologia Molecular de Barcelona, Spain)

In high resolution macromolecular crystallography, the use of small fragments in phasing is currently well established. A small fraction of a structure, if highly accurate, may render phases good enough to allow density modification and autotracing algorithms to complete the structure. The method implemented in ARCIMBOLDO [1] relies on the placement with PHASER [2] of ubiquitous fragments, such as α-helices or libraries of β-sheets,  followed by density modification and autotracing with SHELXE. The same principle, whereby a very incomplete but highly accurate structure, when subject to density modification reveals new elements in the structure holds at resolutions down to 3-4Å. Nevertheless, phasing becomes very challenging. The pattern recognition-based interpretation of an electron density into a model with its refinement implemented in ARP/wARP has been efficiently dealing with model completion in this range of resolution [3]. In ARCIMBOLDO, further development in ARCIMBOLDO_LITE with coil coiled mode, in ARCIMBOLDO_SHREDDER and integrating anomalous signal allowed also to address this scenario [4]. With SEQUENCE_SLIDER, impossibility to expand is overcome by improving the polyalanine chains by assembling and refining the most probable side chain conformations. Sequence hypotheses may be generated on a secondary structure basis or using the optimum alignment between a remote homologous structure and target sequences.

[1]: Sammito, M.D. et al. (2016). Acta Crystallogr. Sect. Found. Adv. 72, s23.

[2]: McCoy, A.J. et al., (2007). J. Appl. Cryst. ​ 40​​ , 658–674.