Journal of Chemical Information and Modeling 最新文献

{"title":"Challenge for Deep Learning: Protein Structure Prediction of Ligand-Induced Conformational Changes at Allosteric and Orthosteric Sites.","authors":"Gustav Olanders, Giulia Testa, Alessandro Tibo, Eva Nittinger, Christian Tyrchan","doi":"10.1021/acs.jcim.4c01475","DOIUrl":"https://doi.org/10.1021/acs.jcim.4c01475","url":null,"abstract":"<p><p>In the realm of biomedical research, understanding the intricate structure of proteins is crucial, as these structures determine how proteins function within our bodies and interact with potential drugs. Traditionally, methods like X-ray crystallography and cryo-electron microscopy have been used to unravel these structures, but they are often challenging, time-consuming and costly. Recently, a breakthrough in computational biology has emerged with the development of deep learning algorithms capable of predicting protein structures based on their amino acid sequences (Jumper, J., et al. <i>Nature</i> <b>2021</b>, <i>596</i>, 583. Lane, T. J. <i>Nature Methods</i> <b>2023</b>, <i>20</i>, 170. Kryshtafovych, A., et al. <i>Proteins: Structure, Function and Bioinformatics</i> <b>2021</b>, <i>89</i>, 1607). This study focuses on predicting the dynamic changes that proteins undergo upon ligand binding, specifically when they bind to allosteric sites, i.e. a pocket different from the active site. Allosteric modulators are particularly important for drug discovery, as they open new avenues for designing drugs that can target proteins more effectively and with fewer side effects (Nussinov, R.; Tsai, C. J. <i>Cell</i> <b>2013</b>, <i>153</i>, 293). To study this, we curated a data set of 578 X-ray structures comprised of proteins displaying orthosteric and allosteric binding as well as a general framework to evaluate deep learning-based structure prediction methods. Our findings demonstrate the potential and current limitations of deep learning methods, such as AlphaFold2 (Jumper, J., et al. <i>Nature</i> <b>2021</b>, <i>596</i>, 583), NeuralPLexer (Qiao, Z., et al. <i>Nat Mach Intell</i> <b>2024</b>, <i>6</i>, 195), and RoseTTAFold All-Atom (Krishna, R., et al. <i>Science</i> <b>2024</b>, <i>384</i>, eadl2528) to predict not just static protein structures but also the dynamic conformational changes. Herein we show that predicting the allosteric induce-fit conformation still poses a challenge to deep learning methods as they more accurately predict the orthosteric bound conformation compared to the allosteric induce fit conformation. For AlphaFold2, we observed that conformational diversity, and sampling between the apo and holo state could be increased by modifying the MSA depth, but this did not enhance the ability to generate conformations close to the allosteric induced-fit conformation. To further support advancements in protein structure prediction field, the curated data set and evaluation framework are made publicly available.</p>","PeriodicalId":44,"journal":{"name":"Journal of Chemical Information and Modeling ","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"International Day of Charity: what does charity mean for diabetes?","authors":"David Beran, Stéphane Besançon","doi":"10.1016/S2213-8587(24)00281-X","DOIUrl":"10.1016/S2213-8587(24)00281-X","url":null,"abstract":"","PeriodicalId":44,"journal":{"name":"Journal of Chemical Information and Modeling ","volume":" ","pages":"787-788"},"PeriodicalIF":44.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A molecular mechanism for bright color variation in parrots","authors":"Roberto Arbore,&nbsp;Soraia Barbosa,&nbsp;Jindich Brejcha,&nbsp;Yohey Ogawa,&nbsp;Yu Liu,&nbsp;Michaël P. J. Nicolaï,&nbsp;Paulo Pereira,&nbsp;Stephen J. Sabatino,&nbsp;Alison Cloutier,&nbsp;Emily Shui Kei Poon,&nbsp;Cristiana I. Marques,&nbsp;Pedro Andrade,&nbsp;Gerben Debruyn,&nbsp;Sandra Afonso,&nbsp;Rita Afonso,&nbsp;Shatadru Ghosh Roy,&nbsp;Uri Abdu,&nbsp;Ricardo J. Lopes,&nbsp;Peter Mojzeš,&nbsp;Petr Marík,&nbsp;Simon Yung Wa Sin,&nbsp;Michael A. White,&nbsp;Pedro M. Araújo,&nbsp;Joseph C. Corbo,&nbsp;Miguel Carneiro","doi":"10.1126/science.adp7710","DOIUrl":"10.1126/science.adp7710","url":null,"abstract":"<div >Parrots produce stunning plumage colors through unique pigments called psittacofulvins. However, the mechanism underlying their ability to generate a spectrum of vibrant yellows, reds, and greens remains enigmatic. We uncover a unifying chemical basis for a wide range of parrot plumage colors, which result from the selective deposition of red aldehyde- and yellow carboxyl-containing psittacofulvin molecules in developing feathers. Through genetic mapping, biochemical assays, and single-cell genomics, we identified a critical player in this process, the aldehyde dehydrogenase <i>ALDH3A2</i>, which oxidizes aldehyde psittacofulvins into carboxyl forms in late-differentiating keratinocytes during feather development. The simplicity of the underlying molecular mechanism, in which a single enzyme influences the balance of red and yellow pigments, offers an explanation for the exceptional evolutionary lability of parrot coloration.</div>","PeriodicalId":44,"journal":{"name":"Journal of Chemical Information and Modeling ","volume":"386 6721","pages":""},"PeriodicalIF":44.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to Lancet Diabetes Endocrinol 2024; 12: 39-50.","authors":"","doi":"10.1016/S2213-8587(24)00288-2","DOIUrl":"10.1016/S2213-8587(24)00288-2","url":null,"abstract":"","PeriodicalId":44,"journal":{"name":"Journal of Chemical Information and Modeling ","volume":" ","pages":"e20"},"PeriodicalIF":44.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"News at a glance.","authors":"","doi":"10.1126/science.adu2388","DOIUrl":"10.1126/science.adu2388","url":null,"abstract":"","PeriodicalId":44,"journal":{"name":"Journal of Chemical Information and Modeling ","volume":"386 6721","pages":"470-471"},"PeriodicalIF":44.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alzheimer's drug approvals create prescribing dilemmas.","authors":"Jennifer Couzin-Frankel","doi":"10.1126/science.adu2383","DOIUrl":"10.1126/science.adu2383","url":null,"abstract":"<p><p>Clinicians and patients weigh modest benefits of the antibodies against sometimes-serious side effects.</p>","PeriodicalId":44,"journal":{"name":"Journal of Chemical Information and Modeling ","volume":"386 6721","pages":"472-473"},"PeriodicalIF":44.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"You won't believe this.","authors":"Kai Kupferschmidt","doi":"10.1126/science.adu2101","DOIUrl":"10.1126/science.adu2101","url":null,"abstract":"<p><p>Researchers are trying to \"inoculate\" people against misinformation by giving them small doses.</p>","PeriodicalId":44,"journal":{"name":"Journal of Chemical Information and Modeling ","volume":"386 6721","pages":"483-485"},"PeriodicalIF":44.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bright dipolar excitons in twisted black phosphorus homostructures","authors":"Shenyang Huang,&nbsp;Boyang Yu,&nbsp;Yixuan Ma,&nbsp;Chenghao Pan,&nbsp;Junwei Ma,&nbsp;Yuxuan Zhou,&nbsp;Yaozhenghang Ma,&nbsp;Ke Yang,&nbsp;Hua Wu,&nbsp;Yuchen Lei,&nbsp;Qiaoxia Xing,&nbsp;Lei Mu,&nbsp;Jiasheng Zhang,&nbsp;Yanlin Mou,&nbsp;Hugen Yan","doi":"10.1126/science.adq2977","DOIUrl":"10.1126/science.adq2977","url":null,"abstract":"<div >Bright dipolar excitons, which contain electrical dipoles and have high oscillator strength, are an ideal platform for studying correlated quantum phenomena. They usually rely on carrier tunneling between two quantum wells or two layers to hybridize with nondipolar excitons to gain oscillator strength. In this work, we uncovered a new type of bright infrared dipolar exciton by stacking 90°-twisted black phosphorus (BP) structures. These excitons, inherent to the reconstructed band structure, exhibit high oscillator strength. Most importantly, they inherit the linear polarization from BP, which allows light polarization to be used to select the dipole direction. Moreover, the dipole moment and resonance energy can be widely tuned by the thickness of the BP. Our results demonstrate a useful platform for exploring tunable correlated dipolar excitons.</div>","PeriodicalId":44,"journal":{"name":"Journal of Chemical Information and Modeling ","volume":"386 6721","pages":""},"PeriodicalIF":44.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cooperative adsorbate binding catalyzes high-temperature hydrogen oxidation on palladium","authors":"Michael Schwarzer,&nbsp;Dmitriy Borodin,&nbsp;Yingqi Wang,&nbsp;Jan Fingerhut,&nbsp;Theofanis N. Kitsopoulos,&nbsp;Daniel J. Auerbach,&nbsp;Hua Guo,&nbsp;Alec M. Wodtke","doi":"10.1126/science.adk1334","DOIUrl":"10.1126/science.adk1334","url":null,"abstract":"<div >Atomic-scale structures that account for the acceleration of reactivity by heterogeneous catalysts often form only under reaction conditions of high temperatures and pressures, making them impossible to observe with low-temperature, ultra-high-vacuum methods. We present velocity-resolved kinetics measurements for catalytic hydrogen oxidation on palladium over a wide range of surface concentrations and at high temperatures. The rates exhibit a complex dependence on oxygen coverage and step density, which can be quantitatively explained by a density functional and transition-state theory–based kinetic model involving a cooperatively stabilized configuration of at least three oxygen atoms at steps. Here, two oxygen atoms recruit a third oxygen atom to a nearby binding site to produce an active configuration that is far more reactive than isolated oxygen atoms. Thus, hydrogen oxidation on palladium provides a clear example of how reactivity can be enhanced on a working catalyst.</div>","PeriodicalId":44,"journal":{"name":"Journal of Chemical Information and Modeling ","volume":"386 6721","pages":""},"PeriodicalIF":44.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to sugar rationing in the first 1000 days of life protected against chronic disease","authors":"Tadeja Gracner, Claire Boone, Paul J. Gertler","doi":"10.1126/science.adn5421","DOIUrl":"https://doi.org/10.1126/science.adn5421","url":null,"abstract":"We examined the impact of sugar exposure within 1000 days since conception on diabetes and hypertension, leveraging quasi-experimental variation from the end of the United Kingdom’s sugar rationing in September 1953. Rationing restricted sugar intake to levels within current dietary guidelines, yet consumption nearly doubled immediately post-rationing. Using an event study design with UK Biobank data comparing adults conceived just before or after rationing ended, we found that early-life rationing reduced diabetes and hypertension risk by about 35% and 20%, respectively, and delayed disease onset by 4 and 2 years. Protection was evident with in-utero exposure and increased with postnatal sugar restriction, especially after six months when solid foods likely began. In-utero sugar rationing alone accounted for about one third of the risk reduction.","PeriodicalId":44,"journal":{"name":"Journal of Chemical Information and Modeling ","volume":"38 1","pages":""},"PeriodicalIF":56.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}