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<jats:title>Visualizing halogen bonding</jats:title> <jats:p> Even though halogen atoms are highly electronegative, a noncovalent bond can form between an electron donor and a halogen atom in a covalent bond. Such interactions are facilitated by the formation of electron-depleted regions in the halogen's covalent bond, a situation least likely for fluorine atoms. Han <jats:italic>et al.</jats:italic> used noncontact scanning tunneling microscopy with submolecular resolution to explore how the size and polarizability of halogens affect complex formation by halogenated benzene molecules adsorbed on a silver surface (see the Perspective by Neaton). With the help of density functional theory, they show how several weak interactions, including van der Waals forces, electrostatic repulsions, and halogen bonds, affect structure. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6360" page="206" related-article-type="in-this-issue" vol="358" xlink:href="10.1126/science.aai8625">206</jats:related-article> ; see also p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6360" page="167" related-article-type="in-this-issue" vol="358" xlink:href="10.1126/science.aap7459">167</jats:related-article> </jats:p>

<jats:title>3D texture morphing for camouflage</jats:title> <jats:p> Some animals, such as cephalopods, use soft tissue to change shape reversibly for camouflage and object manipulation. Pikul <jats:italic>et al.</jats:italic> used fixed-length fiber mesh embedded in a silicone elastomer to transform a flat object into a 3D structure by inflating membranes (see the Perspective by Laschi). Painted models of rocks and plants were also created that could be morphed to fully blend into their surroundings. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6360" page="210" related-article-type="in-this-issue" vol="358" xlink:href="10.1126/science.aan5627">210</jats:related-article> ; see also p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6360" page="169" related-article-type="in-this-issue" vol="358" xlink:href="10.1126/science.aao5345">169</jats:related-article> </jats:p>

<jats:title>Teaching an enzyme to switch sites</jats:title> <jats:p> There has been a recent flurry of activity in modifying enzymes to conduct unnatural chemical reactions more cleanly or selectively than synthetic chemical catalysts. Hammer <jats:italic>et al.</jats:italic> now report application of a cytochrome P450 variant to an oxidation that has largely eluded efficient catalysis. They used directed evolution to mutate the enzyme so that it placed oxygen at the less substituted carbon of the C=C double bond in styrenes, forming aldehyde products. They thereby attained opposite site selectivity to that of the widely used palladium-catalyzed Wacker-Tsuji oxidation. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6360" page="215" related-article-type="in-this-issue" vol="358" xlink:href="10.1126/science.aao1482">215</jats:related-article> </jats:p>

<jats:title>A gram-scale route to bryostatin</jats:title> <jats:p> Scientists once accumulated 14 tons of the red, bushy, tufted sea creature <jats:italic>Bugula neritina</jats:italic> to extract 18 grams of bryostatin 1. The macrocyclic organic compound is under study for treatment of HIV, cancer, and Alzheimer's disease but has proven frustratingly scarce. Wender <jats:italic>et al.</jats:italic> report a 29-step chemical synthesis of bryostatin 1 that proceeds in 4.8% overall yield and provides gram quantities of the compound (see the Perspective by Lanman). Intermediates along the pathway can be straightforwardly modified to produce analogs, two of which were prepared en route and studied in vitro. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6360" page="218" related-article-type="in-this-issue" vol="358" xlink:href="10.1126/science.aan7969">218</jats:related-article> ; see also p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6360" page="166" related-article-type="in-this-issue" vol="358" xlink:href="10.1126/science.aao5346">166</jats:related-article> </jats:p>

<jats:title>A radical route from methane to methanol</jats:title> <jats:p> The conversion of methane into chemicals usually proceeds through high-temperature routes that first form more reactive carbon monoxide and hydrogen. Agarwal <jats:italic>et al.</jats:italic> report a low-temperature (50°C) route in aqueous hydrogen peroxide (H <jats:sub>2</jats:sub> O <jats:sub>2</jats:sub> ) for oxidizing methane to methanol in high yield (92%). They used colloidal gold-palladium nanoparticles as a catalyst. The primary oxidant was O <jats:sub>2</jats:sub> ; isotopic labeling showed that H <jats:sub>2</jats:sub> O <jats:sub>2</jats:sub> activated methane to methyl radicals, which subsequently incorporated O <jats:sub>2</jats:sub> . </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6360" page="223" related-article-type="in-this-issue" vol="358" xlink:href="10.1126/science.aan6515">223</jats:related-article> </jats:p>

<jats:title>Measuring the far side of the Galaxy</jats:title> <jats:p> Direct measurements of distances to astronomical sources rely on parallax, which can usually only be measured for relatively nearby objects. The far side of the Milky Way has been impossible to measure accurately, because the parallax is very small and interstellar dust blocks optical light from those regions. Sanna <jats:italic>et al.</jats:italic> used radio interferometry to directly determine the parallax distance to a star-forming region on the far side of the Galaxy. They also used a method of inferring distances from transverse motions, which produced the same answer. This allowed them to trace one of the Milky Way's spiral arms through almost an entire rotation. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6360" page="227" related-article-type="in-this-issue" vol="358" xlink:href="10.1126/science.aan5452">227</jats:related-article> </jats:p>

<jats:title>Forests out of balance</jats:title> <jats:p> Are tropical forests a net source or net sink of atmospheric carbon dioxide? As fundamental a question as that is, there still is no agreement about the answer, with different studies suggesting that it is anything from a sizable sink to a modest source. Baccini <jats:italic>et al.</jats:italic> used 12 years of MODIS satellite data to determine how the aboveground carbon density of woody, live vegetation has changed throughout the entire tropics on an annual basis. They find that the tropics are a net carbon source, with losses owing to deforestation and reductions in carbon density within standing forests being double that of gains resulting from forest growth. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6360" page="230" related-article-type="in-this-issue" vol="358" xlink:href="10.1126/science.aam5962">230</jats:related-article> </jats:p>

<jats:title>A signature event for organoids</jats:title> <jats:p> Human cancer genomes harbor cryptic mutational signatures that represent the cumulative effects of DNA damage and defects in DNA repair processes. Knowledge of how specific signatures originate could have a major impact on cancer diagnosis and prevention. One approach to address this question is to reproduce the signatures in experimental systems by genetic engineering and then match the signatures to those found in naturally occurring cancers. Drost <jats:italic>et al.</jats:italic> used CRISPR-Cas9 to delete certain DNA repair enzymes from human colon organoids. In a proof-of-concept study, they show that deficiency in base excision repair is responsible for a mutational signature previously identified in cancer genome sequencing projects. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6360" page="234" related-article-type="in-this-issue" vol="358" xlink:href="10.1126/science.aao3130">234</jats:related-article> </jats:p>

<jats:title>An expanded view of disordered proteins</jats:title> <jats:p> Disordered proteins sample an ensemble of conformations, but it has remained unclear how compact these conformations are in water. Polymer physics relates the radius of gyration ( <jats:italic>R</jats:italic> <jats:sub>g</jats:sub> ) to solvent quality, with more chain collapse occurring in poorer solvents. Riback <jats:italic>et al.</jats:italic> developed an analysis scheme that allows them to extract solvent quality and <jats:italic>R</jats:italic> <jats:sub>g</jats:sub> from a single small-angle x-ray scattering measurement. Applying this method, they found that even disordered proteins with low net charge and high hydrophobicity remain expanded in water. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6360" page="238" related-article-type="in-this-issue" vol="358" xlink:href="10.1126/science.aan5774">238</jats:related-article> </jats:p>

<jats:p> <jats:fig orientation="portrait" position="anchor"> <jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" orientation="portrait" position="float" xlink:href="358_242b_f1.gif" /> </jats:fig> The 3D structure of a protein defines not only its size and shape but also its function. But the relationship between structure and function is anything but simple. As such, designing drugs to regulate the functions of these proteins remains an arduous goal. Integrative structural biologists—a diverse collection of scientists from various fields such as cell biology, protein engineering, and computational science—use multiple sources of data and a combination of methods to answer intractable structural biology questions. Recent advancements in technology have allowed the structures of macromolecules to be deciphered at greater and greater speeds. However, as new methods are developed, there are challenges to overcome with respect to their integration into the growing suite of applications. Included in this booklet are articles from the Science family of journals, as well as from the booklet sponsor, detailing the analytical tools available and how they can be applied to solve some of the most complex challenges in the field. </jats:p> <jats:p> This special supplement brought to you by the <jats:bold>Science</jats:bold> /AAAS Custom Publishing Office. </jats:p>