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The wwPDB responds to the articleOn the prompt update of literature references in the Protein Data Bank[Wlodawer (2014),Acta Cryst.D70, 2779].

The Protein Data Bank (PDB) contains a wealth of structural and functional knowledge about proteins, RNA, DNA, and other macromolecules, and their assemblies and complexes with small molecules. The challenge faced by the providers of PDB data is to make this knowledge accessible to an increasingly large and diverse audience, ranging from expert structural biologists to non-specialist consumers of structural information. Educators, students, and general audiences will have their own specific interests and expectations from molecular structure data. For a general user, a 2D image of hemoglobin illustrates how a protein looks at a microscopic level. For high school students and educators, 3D models or computer graphics can show how one or a few specific proteins can assemble into an icosahedral virus. In contrast, PhD and post-doc level researchers require expert guidance on how to critically assess the quality of structural data, and in-depth training on the use of specialist tools and resources for the comparison and analysis of structures. The PDB archive is managed by members of the Worldwide Protein Data Bank (wwPDB): the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB; rcsb.org), Protein Data Bank in Europe (PDBe; pdbe.org), Protein Data Bank Japan (PDBj), and BioMagResBank (BMRB, bmrb.wisc.edu). In addition to managing and distributing structural data, the wwPDB partners are engaged in numerous outreach initiatives and user training programs. These efforts are vital to ensuring that these uniquely valuable data can be effectively accessed and used by research scientists, students, and educators alike. This talk will describe on-going wwPDB outreach efforts and highlight exciting new initiatives at the RCSB PDB, PDBe and PDBj.

The Protein Data Bank (PDB) is the single global archive of 3D biomacromolecular structure data. The archive is managed by the Worldwide Protein Data Bank (wwPDB; wwpdb.org) organisation through its partners, the Research Collaboratory for Structural Bioinformatics (RCSB PDB), the Protein Data Bank Japan (PDBj), the Protein Data Bank in Europe and the Biological Magnetic Resonance Bank (BMRB). Analogously, the Electron Microscopy Data Bank (EMDB) is managed by the EMDataBank (emdatabank.org) organisation. A few years ago, realising the needs and opportunities to assess the quality of biomacromolecular structures deposited in the PDB, the wwPDB and EMDataBank partners established Validation Task Forces (VTFs) to advice them on up-to-date and community-agreed methods and standards to validate X-ray, NMR and 3DEM structures and data. All three VTFs have now published their recommendations (1, 2, 3) and these are getting implemented as validation-software pipelines . The pipelines are integrated in the new joint wwPDB deposition and annotation system (http://deposit.wwpdb.org/deposition/). In addition, stand-alone servers are provided to allow practising structural biologists to validate models prior to publication and deposition (http://wwpdb.org/validation-servers.html). The validation pipelines and the output they produce (human-readable PDF reports and machine-readable XML files) will be described.

Acyl-CoA binding protein (ACBP) maintains a pool of fatty acyl-CoA molecules in the cell and plays a role in fatty acid metabolism. The biochemical properties of Plasmodium falciparum ACBP are described together with the 2.0 A resolution crystal structures of a P. falciparum ACBP-acyl-CoA complex and of bovine ACBP in two crystal forms. Overall, the bovine ACBP crystal structures are similar to the NMR structures published previously; however, the bovine and parasite ACBP structures are less similar. The parasite ACBP is shown to have a different ligand-binding pocket, leading to an acyl-CoA binding specificity different from that of bovine ACBP. Several non-conservative differences in residues that interact with the ligand were identified between the mammalian and parasite ACBPs. These, together with measured binding-specificity differences, suggest that there is a potential for the design of molecules that might selectively block the acyl-CoA binding site.

Since the process of building and refining a model of a biomacromolecule based on crystallographic data is subjective, quality-control techniques are required to assess the validity of such models. During the 1990s, much experience was gained; the methods used and some of the lessons learned are reviewed here. In addition, an extensive compendium of quality criteria and quality-control methods that are or have been used to validate models of biomacromolecules has been compiled. The emphasis in this compendium is on the validation of protein crystal structures.

Retinoids play important roles in diverse cellular processes including growth, cell differentiation and vision. Many natural and synthetic retinoids are used as drugs in dermatology and oncology. A large amount of data has been accumulated on the cellular activity of different synthetic retinoids. They are stabilized and transported inside the cell cytoplasm by binding and transport proteins, such as cellular retinol-binding proteins and cellular retinoic acid binding proteins (CRABPs). The structures of human CRABP II in complex with two different synthetic retinoids, Ro13-6307 and Ro12-7310 (at 2.1 and 2.0 Å resolution, respectively) and of bovine CRABP I in complex with a retinobenzoic acid, Am80 (at 2.8 Å resolution) are described. The binding affinities of human CRABP I and II for the retinoids studied here have been determined. All these compounds have comparable binding affinities (nanomolar range) for both CRABPs. Apart from the particular interactions of the carboxylate group of the retinoids with specific protein groups, each structure reveals characteristic interactions. Studying the atomic details of the interaction of retinoids with retinoid-binding proteins facilitates the understanding of the kinetics of retinoid trafficking inside the cytoplasm.

Prior to attaching any biological significance to differences between two related protein crystal structures, it must be established that such differences are genuine, rather than artefacts of the structure-determination protocol. This will be all the more important as more and more related protein structures are solved and comparative structural biology attempts to correlate structural differences with variations in biological function, activity or affinity. A method has been developed which enables unbiased assessment of differences between the structures of related biomacromolecules using experimental crystallographic information alone. It is based on the use of local density-correlation maps, which contain information regarding the similarity of the experimental electron density for corresponding parts of different copies of a molecule. The method can be used to assess a priori which parts of two or more molecules are likely to be structurally similar; this information can then be employed during structure refinement. Alternatively, the method can be used a posteriori to verify that differences observed in two or more models are supported by the experimental information. Several examples are discussed which validate the notion that local conformational variability is highly correlated to differences in the local experimental electron density.

Applications of structural databases in the protein crystallographic structure determination process are reviewed, using mostly examples from work carried out by the authors. Four application areas are discussed: model building, model refinement, model validation and model analysis.

Statistical cross-validation has become an integral part of the model-refinement process in macromolecular crystallography. However, the test set of reflections, for which the free R value is calculated, is used both to optimize the parameterization of the structure model and to validate the model itself. This practice could introduce bias and diminish the value of R(free) as an independent check of model quality. It is proposed here that by introducing a dormant hold-out set of reflections, any problems with such bias can be avoided. This procedure requires only a small modification of the standard cross-validation protocol.

We are writing to address the retraction of five papers on structural studies of ATP-binding cassette (ABC) transporters—three in Science (G. Chang et al. , “Retraction,” Letters, 22 Dec. 2006, p. [1875][1]), one in the Proceedings of the National Academy of Sciences ([1][2]), and one in the

The Protein Data Bank contains a number of structures for which only the coordinates of the Calpha atoms have been deposited. Although many tools are available for the validation of all-atom protein models, hardly any of these can be used to assess the quality of models for which only Calpha coordinates are available. Two rapid and simple tests to assess the quality of the Calpha backbone of a protein model are described, one based on the distribution of Calpha-Calpha distances, and the other on the two-dimensional distribution of the angles and dihedrals formed by sequential Calpha atoms. Expected distributions were derived by analysing a set of 1343 high-resolution, all-atom protein models. The distance criterion is useful to discriminate between refined and unrefined models, whereas the angle/dihedral criterion can be used to discriminate between normal and possibly problematic Calpha models. The method has been applied to a set of 88 Calpha-only models from the Protein Data Bank. The tracing of two of the models that are outliers in this analysis has recently been shown to be incorrect. Other applications of the method are discussed.

A conceptually simple real-space convolution method has been developed which can be used to detect or enhance structural features in experimental macromolecular electron-density maps. The method has been implemented in a computer program (ESSENS). One application of the method is in selectively visualizing secondary-structure elements in multiple isomorphous replacement (MIR) maps of proteins, prior to map interpretation. This application is demonstrated for MIR maps of P2 myelin protein [Jones, Bergfors, Sedzik & Unge (1988). EMBO J. 7, 1597-1604; Cowan, Newcomer & Jones (1993). J. Mol. Biol. 230, 1225-1246] and glyoxalase I [Cameron, Olin, Ridderstrom, Mannervik & Jones (1997). In preparation]. Another application is in finding the optimal orientation and position of a known structural fragment (e.g. a protein domain or a ligand) in any type of electron-density map (real-space or phased molecular replacement). This application is demonstrated for the complex of acetylcholinesterase and the snake toxin fasciculin II [Harel, Kleywegt, Ravelli, Silman & Sussman (1995). Structure, 3, 1355-1366] where the toxin was located in a map phased using the molecular-replacement solution for the acetylcholinesterase alone.

Publisher Summary Model refinement has been a personalized affair for which laboratories have their preferred strategies, programs, etc. This has resulted in models with distinctive features of both the groups concerned and the software used. This chapter discusses the way a macromolecule should be refined and argues that the present practices in the community are often far from optimal, especially when only low-resolution data are available. All refinement programs nowadays use empirical restraints or constraints to ensure that a reasonable structure ensues during the refinement steps. This can result in a model with good stereochemical properties and also in a model in which molecules related by non-crystallographic symmetry (NCS) are forced to have similar (restrained) or identical (constrained) conformations. The aim of model building and refinement should be to construct a model that adequately explains the experimental observations, while making physical, chemical, and biological sense. It is a fact that low-resolution data can yield only low-resolution models. The refinement process, in particular, should always be tailored for each problem individually, keeping in mind the amount, resolution, and quality of the data.

Publisher Summary Detecting similarities at the level of tertiary structure is of interest for at least three reasons—namely, (1) it may provide insight into the modus operandi of proteins that share a common structural and functional trait, (2) it may reveal evolutionary pathways (either divergent or convergent), and (3) it may provide insight into protein folding and stability by revealing that a certain arrangement of helices and strands occurs in unrelated proteins. In all cases, if similarities at the tertiary structure level exist, sequence alignments based on these similarities are important. Such structure-based sequence alignments are expected to correlate with functional similarities. A cluster analysis using several known, high-resolution structures is carried out to find “typical” geometries of consecutive stretches of five Cα atoms in α helices and β strands, respectively.

The Worldwide Protein Data Bank (wwPDB) strongly agrees with the overall views expressed by Joosten et al. (2013 ▶) in their article about timely deposition of macromolecular structures in the Protein Data Bank. In 2010, Acta Crystallographica Section D began to require validation reports as part of the manuscript-submission process. In that same year, the wwPDB sent letters to the key journals that publish structures requesting that they require authors to submit wwPDB validation reports at the same time as their manuscripts. In this way, reviewers are able to better evaluate the work. The Journal of Biological Chemistry, which is currently the journal that publishes the largest number of papers per year about structures of biological macromolecules, began requiring these reports in 2012. Joosten et al. suggest that it would be helpful to have an option to suppress entry titles at the time of submission to the PDB until the structure is released. Policy matters such as this are regularly reviewed by the wwPDB partners and its Advisory Committee (wwPDB AC). The issue was discussed at our 2013 meeting, and it was agreed that we will make this option available in the new wwPDB Deposition Tool that will be launched early in 2014.

A response to the article by Jaskolski [(2013), Acta Cryst. D69, 1865–1866]., The wwPDB responds to the article by Jaskolski [(2013), Acta Cryst. D69, 1865–1866].

Trichoderma reesei cellobiohydrolase II (CBHII) is an exoglucanase cleaving primarily cellobiose units from the non-reducing end of cellulose chains. The β-l,4 glycosidic bond is cleaved by acid catalysis with an aspartic acid, D221, as the likely proton donor, and another aspartate, D175, probably ensuring its protonation and stabilizing charged reaction intermediates. The catalytic base has not yet been identified experimentally. The refined crystal structure of CBHII also shows a tyrosine residue, Y169, located close enough to the scissile bond to be involved in catalysis. The role of this residue has been studied by introducing a mutation Y169F, and analysing the kinetic and binding behaviour of the mutated CBHII. The crystal structure of the mutated enzyme was determined to 2.0 Å resolution showing no changes when compared with the structure of native CBHII. However, the association constants of the mutant enzyme for cellobiose and cellotriose are increased threefold and for 4-methylumbelliferyl cellobioside over 50-fold. The catalytic constants towards cellotriose and cellotetraose are four times lower for the mutant. These data suggest that Y169, on interacting with a glucose ring entering the second subsite in a narrow tunnel, helps to distort the glucose ring into a more reactive conformation. In addition, a change in the pH activity profile was observed. This indicates that Y169 may have asecond role in the catalysis, namely to affect the protonation state of the active site carboxylates, D175 and D221.

Crystals of bovine cellular retinoic acid-binding protein (CRABPI) have been grown from protein expressed in E. coli. Two different crystal forms were obtained. Crystals containing protein with the ligand all-trans retinoic acid belong to space group P4(1) or P4(3), a = b = 41.36, c = 202.71 A and diffract to 2.5 A. Crystals of CRABP with the synthetic retinoid analogue Am80 diffract to 1.9 A with space group P2(1) and cell dimensions a = 37.03, b = 105.93, c = 40.31 A, beta = 110.28 degrees. Considerations in the crystallization of proteins with light-sensitive ligands are discussed.

A computer program, VOIDOO, is described which can be employed in the study of cavities such as they occur in macromolecular structures (in particular, in proteins). The program can be used to detect unknown cavities or to delineate known cavities, either of which may be connected to the outside of the molecule or molecular assembly under study. Optionally, output files can be requested that contain a description of the shape of the cavity which can be displayed by the crystallographic modelling program O. Additionally, VOIDOO can be used to calculate the volume of a molecule and to create a file containing data pertaining to the surface of the molecule which can also be displayed using O. Examples of the use of VOIDOO are given for P2 myelin protein, cellular retinol-binding protein and cellobiohydrolase II. Finally, operational definitions to discern different types of cavity are introduced and guidelines for assessing the accuracy and improving the comparability of cavity calculations are given.

A suite of computer programs (CLAIRE) is described which can be of assistance in the process of assigning 2D 1H NMR spectra of proteins. The programs embody a software implementation of the sequential assignment approach first developed by Wüthrich and co-workers (K. Wüthrich, G. Wider, G. Wagner and W. Braun (1982) J. Mol. Biol. 155, 311). After data-abstraction (peakpicking), the software can be used to detect patterns (spin systems), to find cross peaks between patterns in 2D NOE data sets and to generate assignments that are consistent with all available data and which satisfy a number of constraints imposed by the user. An interactive graphics program called CONPAT is used to control the entire assignment process as well as to provide the essential feedback from the experimental NMR spectra. The algorithms are described in detail and the approach is demonstrated on a set of spectra from the mistletoe protein phoratoxin B, a homolog of crambin. The results obtained compare well with those reported earlier based entirely on a manual assignment process.

Algorithms for the automation of the assignment of two-dimensional proton NMR spectra of proteins are presented. STELLA is a program suite for automatic, semi-automatic or manual peak-picking. CLAIRE is a software package for human-aided assignment. The programs are demonstrated using data sets pertaining to phoratoxin B, a protein consisting of 46 amino-acid residues.

A computer program, PEGASUS (PROLOG-based EXSPEC Generator for Acyclic StrUctureS), has been developed which can be used to generate exhaustively and non-redundantly all possible acyclic isomers that satisfy a given molecular weight or formula PEGASUS was written in PROLOG and implemented on an inexpensive personal computer (Apple Macintosh Plus). The program is described and the scope for its application is surveyed.

The crystal structures of three compounds ML(NO3)2 are described, where M = Cu, Ni, or Cd and L is the tripodal quadridentate ligand tris(3,5-dimethylpyrazol-1-ylmethyl)amine. The structure of the copper compound can best be described as tetragonally distorted trigonal bipyramidal. As in the other compounds, the ligand L utilizes each of its four potential donor sites. One nitrate ion is unidentate, yielding a CuN4O chromophore. In the nickel compound a nitrate ion is symmetrically bidentate, yielding a distorted octahedral cis-NiN4O2 chromophore. In the cadmium compound one of the nitrate ions is unsymmetrically bidentate, the other symmetrically bidentate, yielding a CdN4O3 chromophore. The structure is best described as distorted bicapped octahedral. The nitrate co-ordination modes were investigated using several spectroscopic techniques. Criteria to differentiate between the unidentate, unsymmetrically bidentate, and symmetrically bidentate modes are presented. In this type of compound discrimination between the co-ordination modes solely on the basis of spectroscopic behaviour appears not to be possible. Slight changes in the i.r. spectra of CuL(NO3)2, and of the analogous cobalt and zinc compounds, upon applying pressure can be understood in terms of changes in the nitrate co-ordination.

The use of validation metrics to rank macromolecular structures, as well as a web tool to investigate trends in and correlations between different properties and validation metrics, are described., Realising the importance of assessing the quality of the biomolecular structures deposited in the Protein Data Bank (PDB), the Worldwide Protein Data Bank (wwPDB) partners established Validation Task Forces to obtain advice on the methods and standards to be used to validate structures determined by X-ray crystallography, nuclear magnetic resonance spectroscopy and three-dimensional electron cryo-microscopy. The resulting wwPDB validation pipeline is an integral part of the wwPDB OneDep deposition, biocuration and validation system. The wwPDB Validation Service webserver (https://validate.wwpdb.org) can be used to perform checks prior to deposition. Here, it is shown how validation metrics can be combined to produce an overall score that allows the ranking of macromolecular structures and domains in search results. The ValTrendsDB database provides users with a convenient way to access and analyse validation information and other properties of X-ray crystal structures in the PDB, including investigating trends in and correlations between different structure properties and validation metrics.

Background: Fasciculin (FAS), a 61-residue polypeptide purified from mamba venom, is a three-fingered toxin which is a powerful reversible inhibitor of acetylcholinesterase (AChE). Solution of the three-dimensional structure of the AChE/FAS complex would provide the first structure of a three-fingered toxin complexed with its target.Results The structure of a complex between Torpedo californica AChE and fasciculin-II (FAS-II), from the venom of the green mamba (Dendroaspis angusticeps) was solved by molecular replacement techniques, and refined at 3.0 å resolution to an R-factor of 0.231. The structure reveals a stoichiometric complex with one FAS molecule bound to each AChE subunit. The AChE and FAS conformations in the complex are very similar to those in their isolated structures. FAS is bound at the ‘peripheral’ anionic site of AChE, sealing the narrow gorge leading to the active site, with the dipole moments of the two molecules roughly aligned. The high affinity of FAS for AChE is due to a remarkable surface complementarity, involving a large contact area (∼2000 å2) and many residues either unique to FAS or rare in other three-fingered toxins. The first loop, or finger, of FAS reaches down the outer surface of the thin aspect of the gorge. The second loop inserts into the gorge, with an unusual stacking interaction between Met33 in FAS and Trp279 in AChE. The third loop points away from the gorge, but the C-terminal residue makes contact with the enzyme.Conclusion Two conserved aromatic residues in the AChE peripheral anionic site make important contacts with FAS. The absence of these residues from chicken and insect AChEs and from butyrylcholinesterase explains the very large reduction in the affinity of these enzymes for FAS. Several basic residues in FAS make important contacts with AChE. The complementarity between FAS and AChE is unusual, inasmuch as it involves a number of charged residues, but lacks any intermolecular salt linkages.

GJK thanks Dr T Alwyn Jones for many stimulating discussion concerning model quality, validation and the free R value, and Dr Randy J Read for suggesting the test with a backward-traced model containing NCS. ATB thanks Drs P Adams, FT Burling, P Gros, J-S Jiang, RJ Read, LM Rice, and ALU Roberts for stimulating discussions about cross-validation in crystallography. GJK acknowledges support from Uppsala University and the European Union (through grant number BIO4-CT96-0189 to Dr TA Jones, Uppsala). ATB acknowledges support from the National Science Foundation (grant number BIR-9514819).

We describe the functionality and design of the Volume slicer – a web-based slice viewer for EMDB entries. This tool uniquely provides the facility to view slices from 3D EM reconstructions along the three orthogonal axes and to rapidly switch between them and navigate through the volume. We have employed multiple rounds of user-experience testing with members of the EM community to ensure that the interface is easy and intuitive to use and the information provided is relevant. The impetus to develop the Volume slicer has been calls from the EM community to provide web-based interactive visualisation of 2D slice data. This would be useful for quick initial checks of the quality of a reconstruction. Again in response to calls from the community, we plan to further develop the Volume slicer into a fully-fledged Volume browser that provides integrated visualisation of EMDB and PDB entries from the molecular to the cellular scale.

The global Protein Data Bank (PDB) was the first open-access digital archive in biology. The history and evolution of the PDB are described, together with the ways in which molecular structural biology data and information are collected, curated, validated, archived, and disseminated by the members of the Worldwide Protein Data Bank organization (wwPDB; http://wwpdb.org). Particular emphasis is placed on the role of community in establishing the standards and policies by which the PDB archive is managed day-to-day.

The success of computer-aided methods for the identification or structure elucidation of organic molecules is determined by the reliability of the analytical results, which in many cases can be assessed through the statistical significance of the conclusions. A key factor determining the usefulness of computer-aided library search systems is the extent to which the reproducibility of the relevant data is accounted for in the design of the similarity measure. Based on mathematical statistical models of the reproducibility of the data involved, library search systems for mass, 13C-NMR and high resolution 1H-NMR spectra, as well as for ultra-violet spectra combined with HPLC retention data have been developed (in FORTRAN and Pascal). These systems are accessible (provisionally on an experimental basis) to Dutch universities and other laboratories through the national CASSAM Centre (Computer-Aided Spectroscopic Structure Analysis of Molecules) located at Utrecht. For the analysis of combined infra-red and mass spectral data a pilot version of an expert system has been developed (in PROLOG) using artificial intelligence techniques and information theory. Here too, the significance of results is indicated by numerical (relative) probabilities. General concepts and results are discussed.

The Protein Data Bank (PDB) contains a wealth of small molecule - macro molecule complexes the study of which contribute enormously to our understanding of the interactions. However, exploiting and mining this treasure trove of data requires advanced analysis and retrieval methods that take into account both types of molecules. One such method is PDBeMotif, that has been developed by the Protein Data Bank in Europe (PDBe) at EMBL-EBI. Utilizing a relational database model at the back-end, the data structure represents a network of molecule, residue and motif interactions as well as their relative positions in the sequence and in 3D. The loader applies a number of algorithms to analyse PDB and derive necessary information, such as planarity and aromaticity of the chemical compounds, hydrogen-bonds network, coordination geometry, bond types (including pi electron interactions), 3D structural motifs, sequence domains and families. It collects information about sequence features, motifs and catalytic sites from available Distributed Annotation System (DAS) resources. The web application allows for a wide variety of searches and data analysis including protein motifs with chemical fragments association, protein sites characterisation, correlating properties, hits multiple sequence and 3D alignments. The whole system is released under GPL and available with the source code from http://sourceforge.net/projects/pdbsam and on line at http://www.ebi.ac.uk/pdbe-site/PDBeMotif/

The Protein Data Bank in Europe (pdbe.org) is a founding member of the Worldwide PDB consortium (wwPDB; wwpdb.org) and as such is actively engaged in the deposition, annotation, remediation and dissemination of macromolecular structure data through the single global archive for such data, the PDB. Similarly, PDBe is a member of the EMDataBank organisation (emdatabank.org), which manages the EMDB archive for electron microscopy data. PDBe also develops tools that help the biomedical science community to make effective use of the data in the PDB and EMDB for their research. Here we describe new or improved services, including updated SIFTS mappings to other bioinformatics resources, a new browser for the PDB archive based on Gene Ontology (GO) annotation, updates to the analysis of Nuclear Magnetic Resonance-derived structures, redesigned search and browse interfaces, and new or updated visualisation and validation tools for EMDB entries.

In this thesis, the folding process of the de novo designed polypeptide chignolin was elucidated through atomic-scale Molecular Dynamics (MD) computer simulations. In a series of long timescale and replica exchange MD simulations, chignolin’s folding and unfolding was observed numerous times and the native state was identified from the computed Gibbs free-energy landscape. The rate of the self-assembly process was predicted from the replica exchange data through a novel algorithm and the structural fluctuations of an enzyme, lysozyme, were analyzed. DNA’s structural flexibility was investigated through experimental structure determination methods in the liquid and gas phase. DNA nanostructures could be maintained in a flat geometry when attached to an electrostatically charged, atomically flat surface and imaged in solution with an Atomic Force Microscope. Free in solution under otherwise identical conditions, the origami exhibited substantial compaction, as revealed by small angle X-ray scattering. This condensation was even more extensive in the gas phase. Protein folding is highly reproducible. It can rapidly lead to a stable state, which undergoes moderate fluctuations, at least for small structures. DNA maintains extensive structural flexibility, even when folded into large DNA origami. One may reflect upon the functional roles of proteins and DNA as a consequence of their atomic-level structural flexibility. DNA, biology’s information carrier, is very flexible and malleable, adopting to ever new conformations. Proteins, nature’s machines, faithfully adopt highly reproducible shapes to perform life’s functions robotically.