Brickworx builds recurrent RNA and DNA structural motifs into medium- and low-resolution electron-density maps.

Grzegorz Chojnowski,Wojciech Potrzebowski,Janusz M Bujnicki,Paweł Piątkowski,Tomasz Waleń

doi:10.1107/s1399004715000383

Abstract

Brickworx is a computer program that builds crystal structure models of nucleic acid molecules using recurrent motifs including double-stranded helices. In a first step, the program searches for electron-density peaks that may correspond to phosphate groups; it may also take into account phosphate-group positions provided by the user. Subsequently, comparing the three-dimensional patterns of the P atoms with a database of nucleic acid fragments, it finds the matching positions of the double-stranded helical motifs (A-RNA or B-DNA) in the unit cell. If the target structure is RNA, the helical fragments are further extended with recurrent RNA motifs from a fragment library that contains single-stranded segments. Finally, the matched motifs are merged and refined in real space to find the most likely conformations, including a fit of the sequence to the electron-density map. The Brickworx program is available for download and as a web server at http://iimcb.genesilico.pl/brickworx.

Highlights

The number of experimentally determined structures of nucleic acid molecules, including nucleic acid–protein complexes, is increasing rapidly in line with recent discoveries and growing interest in the biological functions exerted by nucleic acids beyond their protein-coding capacity
For training the support vector machine (SVM) classifier, a set of representative crystal structure models of protein–RNA complexes solved at resolutions between 3.0 and 4.0 Awere selected using nonredundant sets of RNA-containing threedimensional structures (Leontis & Zirbel, 2012)
The program is able to predict the P-atom positions with the help of a support vector machine classifier and can accept positions of P atoms that are specified by the user

Summary

Introduction

The number of experimentally determined structures of nucleic acid molecules, including nucleic acid–protein complexes, is increasing rapidly in line with recent discoveries and growing interest in the biological functions exerted by nucleic acids beyond their protein-coding capacity. Computational tools that automatically build a crystal structure model into an experimental electron-density map are markedly less developed for nucleic acids than for proteins. Automated model-building computer programs doi:10.1107/S1399004715000383 697 research papers can speed up the structure-determination process considerably and help to minimize the amount of errors in modelling (Hattne & Lamzin, 2008). This is important in the case of crystals containing nucleic acids. A few methods have been developed to facilitate manual model building, such as RCrane (Keating & Pyle, 2010) and Coot (Emsley et al, 2010)

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Conclusion