Practical structure solution with 
                     ARCIMBOLDO

Iñaki M. de Ilarduya,George M. Sheldrick,Dayté Rodríguez,Marianus Potratz,Massimo Sammito,Isabel Usón,Kathrin Meindl

doi:10.1107/s0907444911056071

Abstract

Since its release in September 2009, the structure-solution program ARCIMBOLDO, based on the combination of locating small model fragments such as polyalanine α-helices with density modification with the program SHELXE in a multisolution frame, has evolved to incorporate other sources of stereochemical or experimental information. Fragments that are more sophisticated than the ubiquitous main-chain α-helix can be proposed by modelling side chains onto the main chain or extracted from low-homology models, as locally their structure may be similar enough to the unknown one even if the conventional molecular-replacement approach has been unsuccessful. In such cases, the program may test a set of alternative models in parallel against a specified figure of merit and proceed with the selected one(s). Experimental information can be incorporated in three ways: searching within ARCIMBOLDO for an anomalous fragment against anomalous differences or MAD data or finding model fragments when an anomalous substructure has been determined with another program such as SHELXD or is subsequently located in the anomalous Fourier map calculated from the partial fragment phases. Both sources of information may be combined in the expansion process. In all these cases the key is to control the workflow to maximize the chances of success whilst avoiding the creation of an intractable number of parallel processes. A GUI has been implemented to aid the setup of suitable strategies within the various typical scenarios. In the present work, the practical application of ARCIMBOLDO within each of these scenarios is described through the distributed test cases.

Highlights

Dual-space recycling ab initio methods for phasing equal-atom macromolecular structures that assume atomicity require atomic resolution data (Miller et al, 1993; Sheldrick et al, 2001)
Since its release in September 2009, the structure-solution program ARCIMBOLDO, based on the combination of locating small model fragments such as polyalanine -helices with density modification with the program SHELXE in a multisolution frame, has evolved to incorporate other sources of stereochemical or experimental information
Experimental information can be incorporated in three ways: searching within ARCIMBOLDO for an anomalous fragment against anomalous differences or MAD data or finding model fragments when an anomalous substructure has been determined with another program such as SHELXD or is subsequently located in the anomalous Fourier map calculated from the partial fragment phases

Summary

Introduction

Dual-space recycling ab initio methods for phasing equal-atom macromolecular structures that assume atomicity require atomic resolution data (Miller et al, 1993; Sheldrick et al, 2001). Fragment location in combination with density modification has enabled the solution of previously unknown protein structures at resolutions of up to 2 Aand the identification of the correct phases from the figures of merit characterizing the partial main-chain trace of the resulting map through its CC and number of residues traced. This method has been implemented in the program ARCIMBOLDO (Rodrıguez et al, 2009), which combines multisolution location of small (10–14 amino acids) extremely accurate models such as polyalanine -helices with the program Phaser (McCoy et al, 2007) and density modification and autotracing with the program SHELXE (Sheldrick, 2008). Extension to other middleware systems is intended in the future

ARCIMBOLDO uses

Ab initio

Alternative fragments

Control parameters

Configuration GUI

Findings

Conclusion