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HELIX: a new modular nucleic acid crystallization screen
Author(s) -
Viladoms Julia,
Parkinson Gary N.
Publication year - 2014
Publication title -
journal of applied crystallography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.429
H-Index - 162
ISSN - 1600-5767
DOI - 10.1107/s1600576714007407
Subject(s) - crystallization , nucleic acid , protein data bank (rcsb pdb) , oligonucleotide , protein data bank , crystallography , modular design , helix (gastropod) , computer science , phaser , combinatorial chemistry , computational biology , dna , chemistry , protein structure , stereochemistry , biology , biochemistry , programming language , engineering , organic chemistry , ecology , electrical engineering , snail
Crystallization of nucleic acids remains a bottleneck to their structural characterization by X‐ray crystallography. A new 96‐well‐format initial screen for nucleic acids, called HELIX, has been developed at UCL School of Pharmacy, London, on the basis of a detailed analysis of the crystallization conditions from 1450 nucleic acid structures deposited in the Protein Data Bank (PDB), combined with observations and experience acquired in the authors' nucleic acids crystallography laboratory during the crystallization of DNA/RNA quadruplexes and ligand complexes. Despite using traditional buffers, precipitants and salts, the resulting modular screen is designed to offer a variety of approaches to enhance successful crystallization of oligonucleotides with a diverse range of topologies, sequences and molecular weights. HELIX includes a set of 24 conditions divided into four sets that can be mixed (inter‐ and intra‐set) to provide a customizable orthogonal screening tool for experienced users, termed VariX. Additionally, mindful of synchrotron anomalous data collection, cacodylate buffers are avoided in the formulations and an optimized cryocrystallization module is included. This article reviews the crystallization trends and data derived from the PDB and discusses the HELIX screen layout, formulation and results from in‐house crystallization trials.