Structure 14, 801, May 2006 ª2006 Elsevier Ltd All rights reserved DOI 10.1016/j.str.2006.05.005

Editorial

Structural biology stands at a crossroads built of suc-cess. A decade ago, three-dimensional structures ofsingle, relatively small proteins and nucleic acid frag-ments were considered triumphs in themselves. Now,structure determination is becoming more routine formany of these macromolecules, and structural analysisof larger or more complex biological systems is increas-ingly feasible. This trend is exemplified by the recentatomic descriptions of ion channels, rhodopsin, RNApolymerase II, the ribosome, and the multimodular fattyacid synthases. While much work remains to be done,the underlying structural foundation of many core pro-cesses in biology has been determined, or is nearingcompletion.

Despite this progress, many challenges remain aheadfor structural biology. Structures are still rare or nonex-istent for many multicomponent systems and mem-brane proteins such as G-protein coupled receptors.Moreover, large biomolecular assemblies are often tran-sient and heterogeneous, complicating their structuralcharacterization by traditional methods. Even whenstructures are resolved, the link between structure andmechanism is often tenuous, and details about the cou-pling of macromolecular dynamics, thermodynamics,and mechanism are needed to validate and enhancestructural models. In addition, it remains difficult to elu-cidate how structures have evolved, how to control andmodify their properties, and how to design new systems.For a journal called Structure, it is a time to showcasecompelling work in all of these fields.

Structure originally focused on describing the struc-tures of biological molecules, the rules of their folding,and the principles of biomolecular design. The journalhas evolved over the last several years to place a higherpremium on biological function, particularly on struc-ture/function relationships in systems that illuminate bi-ology in eukaryotic organisms. X-ray crystallographyand NMR spectroscopy approaches provide excep-tional insights into biological function, and Structurecontinues to encourage submission of manuscripts de-tailing macromolecular structures and their interactionsat atomic resolution. We favor structural studies that in-clude biochemical and biophysical analyses, since suchstudies vastly augment the impact of structural work, aswell as those reports on structures that deal with two ormore macromolecular components, as these structuresoften provide vital insights into macromolecular interac-tions. Manuscripts restricted to structure determinationof a single entity will usually only merit publication inStructure if the molecule is of unusually high interestor the structure presents a substantial conceptualadvance.

The complexity of systems undergoing structural anal-ysis is increasing. We are excited about the prospect thatstructural biology will continue to contribute to our under-standing of larger and more intricate biological assem-blies, despite the fact that these studies often involve res-olution of static structures at low to moderate resolution.Correspondingly, Structure encourages submission ofstudies using low-resolution crystallography, cryoelec-tron microscopy, and other imaging techniques.

We continue to support theoretical and computationalapproaches that are grounded in structure, especially ifthey are directed at explaining mechanism or evolution,include new experimental results, or are based on signif-icant methodological advances.

Dynamic behavior in biological processes underliesmechanism.NMR spectroscopy,single-moleculefluores-cence, kinetic analysis, and other forms of spectroscopyare particularly well-suited to address directly the link be-tween structure, dynamics, and mechanism. Therefore,Structure encourages submission of studies that utilizethese approaches to monitor biological dynamics.

Fundamental issues still exist with respect to how bio-logical macromolecules achieve their native, folded state.Reports detailing experimental or computational studiesthat address folding, misfolding, and their role in biologi-cal function and disease remain an interest of the journal.

Finally, the abundant success of structural biologyhas been driven by extraordinary technological ad-vances in x-ray crystallography, NMR spectroscopy,and electron microscopy. This trend will only grow,and Structure promotes publishing significant method-ological advances in these and other emerging struc-tural biology techniques, chiefly through our TechnicalAdvances and Ways & Means formats.

From x-ray crystallography, NMR spectroscopy, andelectron microscopy to protein folding and conforma-tional dynamics, and from significant new biologicalinsights to technical advances and computational ap-proaches, Structure aims to present structural and mo-lecular biologists with a full spectrum of exciting and in-novative research. As both Editors and active scientistsworking in the field, together with the Associate Editor lo-cated in the Cell Press offices, we are committed to pro-viding a home for structural biology research where au-thors receive constructive reviews from their peers ina timely way with rapid publication of accepted papers.

The future of Structure and structure are intimatelylinked. As methods for structural determination have be-come more developed, and, in some cases, automated,the barrier for entry into the world of structure has beenlowered, thus enabling scientists who would not de-scribe themselves as structural biologists to incorporatestructure determination as a tool in their investigativetoolbox. These advances have also allowed many struc-tural biologists to investigate more complex biologicalsystems with an expanded repertoire of experiments.The broad definition of structural biology outlined here,rooted in more traditional structural studies and embrac-ing a wide range of approaches that includes molecularbiology, single-molecule spectroscopy, force measure-ments, and computational approaches, underscoresour central conviction that a combination of techniquesaimed at elucidating the atomic and molecular underpin-nings of macromolecular function will afford the greatestopportunities for understanding biological systems.

Chris Lima, Editor

Joseph D. Puglisi, EditorAndrej Sali, Editor

Lara Szewczak, Associate Editor