-
EMBO Reports Jun 2004Biology's various affairs with holism and reductionism, and their contribution to understanding life at the molecular level (Review)
Review
Biology's various affairs with holism and reductionism, and their contribution to understanding life at the molecular level
Topics: History, 19th Century; History, 20th Century; Macromolecular Substances; Models, Biological; Molecular Biology; Probability
PubMed: 15170468
DOI: 10.1038/sj.embor.7400180 -
Molecular Systems Biology Apr 2023Accurately modeling the structures of proteins and their complexes using artificial intelligence is revolutionizing molecular biology. Experimental data enable a...
Accurately modeling the structures of proteins and their complexes using artificial intelligence is revolutionizing molecular biology. Experimental data enable a candidate-based approach to systematically model novel protein assemblies. Here, we use a combination of in-cell crosslinking mass spectrometry and co-fractionation mass spectrometry (CoFrac-MS) to identify protein-protein interactions in the model Gram-positive bacterium Bacillus subtilis. We show that crosslinking interactions prior to cell lysis reveals protein interactions that are often lost upon cell lysis. We predict the structures of these protein interactions and others in the SubtiWiki database with AlphaFold-Multimer and, after controlling for the false-positive rate of the predictions, we propose novel structural models of 153 dimeric and 14 trimeric protein assemblies. Crosslinking MS data independently validates the AlphaFold predictions and scoring. We report and validate novel interactors of central cellular machineries that include the ribosome, RNA polymerase, and pyruvate dehydrogenase, assigning function to several uncharacterized proteins. Our approach uncovers protein-protein interactions inside intact cells, provides structural insight into their interaction interfaces, and is applicable to genetically intractable organisms, including pathogenic bacteria.
Topics: Proteomics; Artificial Intelligence; Proteins; Mass Spectrometry; Molecular Biology
PubMed: 36815589
DOI: 10.15252/msb.202311544 -
Chemical Reviews Jun 2017Efficient access to chemical information contained in scientific literature, patents, technical reports, or the web is a pressing need shared by researchers and patent... (Review)
Review
Efficient access to chemical information contained in scientific literature, patents, technical reports, or the web is a pressing need shared by researchers and patent attorneys from different chemical disciplines. Retrieval of important chemical information in most cases starts with finding relevant documents for a particular chemical compound or family. Targeted retrieval of chemical documents is closely connected to the automatic recognition of chemical entities in the text, which commonly involves the extraction of the entire list of chemicals mentioned in a document, including any associated information. In this Review, we provide a comprehensive and in-depth description of fundamental concepts, technical implementations, and current technologies for meeting these information demands. A strong focus is placed on community challenges addressing systems performance, more particularly CHEMDNER and CHEMDNER patents tasks of BioCreative IV and V, respectively. Considering the growing interest in the construction of automatically annotated chemical knowledge bases that integrate chemical information and biological data, cheminformatics approaches for mapping the extracted chemical names into chemical structures and their subsequent annotation together with text mining applications for linking chemistry with biological information are also presented. Finally, future trends and current challenges are highlighted as a roadmap proposal for research in this emerging field.
Topics: Chemistry; Data Mining; Documentation; Technology
PubMed: 28475312
DOI: 10.1021/acs.chemrev.6b00851 -
Chemical Reviews Sep 2018
Topics: Carbohydrates; Chemical Phenomena; Chemistry, Organic
PubMed: 30205688
DOI: 10.1021/acs.chemrev.8b00512 -
Biochemical Society Transactions Feb 2021Facilitated by advances in the separation sciences, mass spectrometry and informatics, glycoproteomics, the analysis of intact glycopeptides at scale, has recently... (Review)
Review
Facilitated by advances in the separation sciences, mass spectrometry and informatics, glycoproteomics, the analysis of intact glycopeptides at scale, has recently matured enabling new insights into the complex glycoproteome. While diverse quantitative glycoproteomics strategies capable of mapping monosaccharide compositions of N- and O-linked glycans to discrete sites of proteins within complex biological mixtures with considerable sensitivity, quantitative accuracy and coverage have become available, developments supporting the advancement of structure-focused glycoproteomics, a recognised frontier in the field, have emerged. Technologies capable of providing site-specific information of the glycan fine structures in a glycoproteome-wide context are indeed necessary to address many pending questions in glycobiology. In this review, we firstly survey the latest glycoproteomics studies published in 2018-2020, their approaches and their findings, and then summarise important technological innovations in structure-focused glycoproteomics. Our review illustrates that while the O-glycoproteome remains comparably under-explored despite the emergence of new O-glycan-selective mucinases and other innovative tools aiding O-glycoproteome profiling, quantitative glycoproteomics is increasingly used to profile the N-glycoproteome to tackle diverse biological questions. Excitingly, new strategies compatible with structure-focused glycoproteomics including novel chemoenzymatic labelling, enrichment, separation, and mass spectrometry-based detection methods are rapidly emerging revealing glycan fine structural details including bisecting GlcNAcylation, core and antenna fucosylation, and sialyl-linkage information with protein site resolution. Glycoproteomics has clearly become a mainstay within the glycosciences that continues to reach a broader community. It transpires that structure-focused glycoproteomics holds a considerable potential to aid our understanding of systems glycobiology and unlock secrets of the glycoproteome in the immediate future.
Topics: Glycomics; Glycopeptides; Glycoproteins; Glycosylation; Humans; Protein Conformation; Proteomics
PubMed: 33439247
DOI: 10.1042/BST20200222 -
Proceedings of the National Academy of... Jul 2012
Topics: DNA; Electrochemistry; History, 20th Century; History, 21st Century; Microelectrodes; Nanostructures; Photochemistry
PubMed: 22802653
DOI: 10.1073/pnas.1209943109 -
Current Biology : CB Apr 2004Stuart Schreiber is an Investigator at the Howard Hughes Medical Institute and Morris Loeb Professor in the Department of Chemistry and Chemical Biology at Harvard...
Stuart Schreiber is an Investigator at the Howard Hughes Medical Institute and Morris Loeb Professor in the Department of Chemistry and Chemical Biology at Harvard University. His chemical biology research, which uses small molecules derived from diversity-oriented synthesis, observational screens and information science, has uncovered principles that underlie information transfer and storage in cells. Harvard's ICCB and its affiliated, NCI-sponsored Initiative for Chemical Genetics and the NIGMS-sponsored Center of Excellence in Chemical Methodologies and Library Development are facilitating his research.
Topics: Career Choice; Chemistry, Organic; Information Science; Molecular Biology
PubMed: 15084293
DOI: 10.1016/j.cub.2004.03.044 -
Essays in Biochemistry Oct 2017Within every living organism, countless reactions occur every second. These reactions typically occur more rapidly and with greater efficiency than would be possible... (Review)
Review
Within every living organism, countless reactions occur every second. These reactions typically occur more rapidly and with greater efficiency than would be possible under the same conditions in the chemical laboratory, and while using only the subset of elements that are readily available in nature. Despite these apparent differences between life and the laboratory, biological reactions are governed by the same rules as any other chemical reaction. Thus, a firm understanding of the fundamentals of chemistry is invaluable in biochemistry. There are entire textbooks devoted to the application of chemical principles in biological systems and so it is not possible to cover all of the relevant topics in depth in this short article. The aim is instead to provide a brief overview of those areas in chemistry that are most relevant to biochemistry. We summarize the basic principles, give examples of how these principles are applied in biological systems and suggest further reading on individual topics.
Topics: Animals; Biochemistry; Humans; Metabolome; Organic Chemicals; Organic Chemistry Phenomena
PubMed: 28951470
DOI: 10.1042/EBC20160094 -
Nature Protocols Nov 2015Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) chemistries exploit small electrophilic reagents that react with 2'-hydroxyl groups to interrogate...
Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) chemistries exploit small electrophilic reagents that react with 2'-hydroxyl groups to interrogate RNA structure at single-nucleotide resolution. Mutational profiling (MaP) identifies modified residues by using reverse transcriptase to misread a SHAPE-modified nucleotide and then counting the resulting mutations by massively parallel sequencing. The SHAPE-MaP approach measures the structure of large and transcriptome-wide systems as accurately as can be done for simple model RNAs. This protocol describes the experimental steps, implemented over 3 d, that are required to perform SHAPE probing and to construct multiplexed SHAPE-MaP libraries suitable for deep sequencing. Automated processing of MaP sequencing data is accomplished using two software packages. ShapeMapper converts raw sequencing files into mutational profiles, creates SHAPE reactivity plots and provides useful troubleshooting information. SuperFold uses these data to model RNA secondary structures, identify regions with well-defined structures and visualize probable and alternative helices, often in under 1 d. SHAPE-MaP can be used to make nucleotide-resolution biophysical measurements of individual RNA motifs, rare components of complex RNA ensembles and entire transcriptomes.
Topics: Acylation; Computational Biology; Models, Molecular; Molecular Biology; Mutation; Nucleic Acid Conformation; RNA; RNA Processing, Post-Transcriptional
PubMed: 26426499
DOI: 10.1038/nprot.2015.103 -
Chimia Dec 2020Due to its long half-life of 2.111×10 y, technetium, Tc, offers the excellent opportunity of combining fundamental and ' classical ' organometallic or coordination... (Review)
Review
Due to its long half-life of 2.111×10 y, technetium, Tc, offers the excellent opportunity of combining fundamental and ' classical ' organometallic or coordination chemistry with all methodologies of radiochemistry. Technetium chemistry is inspired by the applications of its short-lived metastable isomer Tc in molecular imaging and radiopharmacy. We present in this article examples about these contexts and the impact of purely basic oriented research on practical applications. This review shows how the chemistry of this element in the middle of the periodic system inspires the chemistry of neighboring elements such as rhenium. Reasons are given for the frequent observation that the chemistries of Tc and Tc are often not identical, compounds accessible for Tc, under certain conditions, are not accessible for Tc. The article emphasizes the importance of macroscopic technetium chemistry not only for research but also for advanced education in the general fields of radiochemistry.
Topics: Molecular Imaging; Radiochemistry; Radiopharmaceuticals; Rhenium; Technetium
PubMed: 33357288
DOI: 10.2533/chimia.2020.953