Abstract：
:In recent years pharmaceutical companies have utilized structure-based drug design and combinatorial library design techniques to speed up their drug discovery efforts. Both approaches are routinely used in the lead discovery and lead optimization stages of the drug discovery process. Fragment-based drug design, a new power tool in the drug design toolbox, is also gaining acceptance across the pharmaceutical industry. This review will focus on the interplay between these three design techniques and recent developments in computational methodologies that enhance their integration. Examples of successful synergistic applications of these three techniques will be highlighted. Opinion regarding possible future directions of the field will be given.
journal_name
Curr Opin Chem Bioljournal_title
Current opinion in chemical biologyauthors
Zhou JZdoi
10.1016/j.cbpa.2008.02.007subject
Has Abstractpub_date
2008-06-01 00:00:00pages
379-85issue
3eissn
1367-5931issn
1879-0402pii
S1367-5931(08)00034-3journal_volume
12pub_type
杂志文章,评审abstract：:Exacerbation of climate change and air pollution around the world have emphasized the necessity of replacing fossil fuels with clean and sustainable energy. Metabolic engineering has provided strategies to engineer diverse organisms for the production of biofuels from renewable carbon sources. Although some of the pro...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2020.02.009
更新日期：2020-12-01 00:00:00
abstract：:Life on Earth originated and evolved in anoxic environments. Around 2.4 billion-years-ago, ancestors of Cyanobacteria invented oxygenic photosynthesis, producing substantial amounts of O2 as a byproduct of phototrophic water oxidation. The sudden appearance of O2 would have led to significant oxidative stress due to i...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2016.03.013
更新日期：2016-04-01 00:00:00
abstract：:The first photocaged complexes appeared in the mid-1980s specifically to complement the ongoing work studying intracellular Ca(2+) signaling with fluorescent probes. Recently, the field of biological inorganic chemistry has focused increasingly on the homeostasis mechanisms and possible signaling functions of transiti...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2012.11.015
更新日期：2013-04-01 00:00:00
abstract：:Recent studies of moonlighting functions and catalytic promiscuity provide insights into the structural and mechanistic bases of these phenomena. Moonlighting proteins that are highlighted include gephyrin, the Neurospora crassa tyrosyl tRNA synthetase, phosphoglucose isomerase, and cytochrome c. New insights into cat...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(03)00032-2
更新日期：2003-04-01 00:00:00
abstract：:Lipids are a vital class of molecules that play important and varied roles in biological processes, however, fully understanding these roles is extremely difficult due to the immense number and diversity of possible lipid species. While recent advances in chromatography and high resolution mass spectrometry have great...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.11.009
更新日期：2018-02-01 00:00:00
abstract：:In many species, double-stranded RNA can specifically and effectively silence genes. This newly discovered biological phenomenon, called RNA interference (RNAi), has practical implications for functional genomics. As shown by two recent reports, RNAi provides a rapid method to test the function of genes in the nematod...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(00)00173-3
更新日期：2001-02-01 00:00:00
abstract：:Metallodrugs are extensively used to treat and diagnose distinct disease types. The unique physical-chemical properties of metal ions offer tantalizing opportunities to tailor effective scaffolds for selectively targeting specific biomolecules. Modern experimental techniques have collected a large body of structural d...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2020.07.005
更新日期：2020-08-08 00:00:00
abstract：:Lipids are indispensable cellular building blocks, and their post-translational attachment to proteins makes them important regulators of many biological processes. Dysfunction of protein lipidation is also implicated in many pathological states, yet its systematic analysis presents significant challenges. Thanks to i...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2020.10.002
更新日期：2020-11-19 00:00:00
abstract：:Molecular oxygen plays an indispensable role as a terminal electron acceptor in the electron transport chain in mitochondria. Acute or chronic oxygen deprivation (hypoxia) in organisms results in various diseases, and the elucidation of the pathogenic mechanism of hypoxia-related diseases and various cellular response...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2016.05.017
更新日期：2016-08-01 00:00:00
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journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
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更新日期：1998-02-01 00:00:00
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journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2009.06.022
更新日期：2009-10-01 00:00:00
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journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2015.01.024
更新日期：2015-04-01 00:00:00
abstract：:Developing technologies such as unnatural amino acid mutagenesis, non-natural cofactor engineering, and computational design are generating proteins with novel functions; these proteins, however, often do not reach performance targets and would benefit from further optimization. Evolutionary methods can complement the...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2010.11.020
更新日期：2011-04-01 00:00:00
abstract：:The site specific, co-translational introduction of unnatural amino acids into proteins produced in cells has been facilitated by the development of the pyrrolysyl-tRNA synthetase/tRNACUA pair. This pair can now be used to direct the site-specific incorporation of designer amino acids in E. coli, yeast, mammalian cell...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2014.07.001
更新日期：2014-08-01 00:00:00
abstract：:Polyketides are a large class of structurally diverse, biologically active natural products. Recent experiments add evidence that many of the enzymes involved in the biosynthesis of these natural products are intrinsically tolerant of nonnatural substrates. In addition, an increasing understanding of structure-functio...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(02)00360-5
更新日期：2002-12-01 00:00:00
abstract：:The field of computational protein design is reaching its adolescence. Protein design algorithms have been applied to design or engineer proteins that fold, fold faster, catalyze, catalyze faster, signal, and adopt preferred conformational states. Further developments of scoring functions, sampling strategies, and opt...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(01)00267-8
更新日期：2001-12-01 00:00:00
abstract：:In recent years, an increasing number of proteins have been discovered which utilize heme cofactors to sense oxygen, carbon monoxide and nitric oxide. The identification and characterization of these proteins are revising our understanding of heme-mediated allostery first established in the early 1960s. Biochemical an...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(00)00193-9
更新日期：2001-04-01 00:00:00
abstract：:Recent structural information suggests that the HC(X)5R active-site motif defines three distinct evolutionary families of phosphatases that employ a common catalytic mechanism. In two instances, regulation of phosphatase activity employs autoinhibitory mechanisms involving either intermolecular or intramolecular inter...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(98)80095-1
更新日期：1998-10-01 00:00:00
abstract：:Sugar nucleotide-modifying enzymes of the short-chain dehydrogenase/reductase type use transient oxidation-reduction by a tightly bound nicotinamide cofactor as a common strategy of catalysis to promote a diverse set of reactions, including decarboxylation, single- or double-site epimerization, and dehydration. Althou...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2020.09.010
更新日期：2020-11-06 00:00:00
abstract：:Different strategies for the creation of optical sensors with metal-dye complexes are discussed. The focus is on sensors, which are used in conjunction with pattern recognition protocols. It is shown that remarkably powerful sensors can be obtained by combining commercially available dyes with simple transition metal ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2010.07.005
更新日期：2010-12-01 00:00:00
abstract：:The micro-environment in which stem cells reside regulates their fate, and synthetic materials have recently been designed to emulate these regulatory processes for various medical applications. Ligands inspired by the natural extracellular matrix, cell-cell contacts, and growth factors have been incorporated into syn...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2007.05.030
更新日期：2007-08-01 00:00:00
abstract：:Given the correlation between many human diseases and mis-regulated transcription, there is a growing need for molecules that can inhibit or mimic key interactions between transcriptional activators and their binding partners. Because transcriptional activators typically participate in many different protein-protein b...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2005.08.012
更新日期：2005-10-01 00:00:00
abstract：:Extracellular electron transfer via filamentous protein appendages called 'microbial nanowires' has long been studied in Geobacter and other bacteria because of their crucial role in globally-important environmental processes and their applications for bioenergy, biofuels, and bioelectronics. Thousands of papers thoug...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2020.08.004
更新日期：2020-12-01 00:00:00
abstract：:Complex glycans participate in many essential life processes. Studies of glycan-mediated biological events have traditionally employed structurally defined fragments of the more elaborate natural molecules. However, it is now clear that this approach may sometimes be insufficient and this realization has prompted a de...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2013.10.009
更新日期：2013-12-01 00:00:00
abstract：:The ability of cobalamin to coordinate different upper axial ligands gives rise to a diversity of reactivity. Traditionally, adenosylcobalamin is associated with radical-based rearrangements, and methylcobalamin with methyl cation transfers. Recently, however, a new role for adenosylcobalamin has been discovered as a ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.01.013
更新日期：2017-04-01 00:00:00
abstract：:Recent advances in membrane protein crystallography have greatly increased structural information of channels permeating metal ions. Structural bioinformatics techniques and molecular dynamics calculations are providing structural models of ion channels for which the three-dimensional structure is not known. Most of t...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(02)00012-1
更新日期：2003-02-01 00:00:00
abstract：:The reactive oxygen and nitrogen species superoxide ion, nitric oxide, nitrogen dioxide and peroxynitrite ion all react with biological target molecules. Some of these interactions are carefully orchestrated segments of signal transduction cascades or part of the armamentarium of the immune system, others are patholog...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/S1367-5931(99)80036-2
更新日期：1999-04-01 00:00:00
abstract：:Metabolomics and lipidomics aim to comprehensively measure the dynamic changes of all metabolites and lipids that are present in biological systems. The use of ion mobility-mass spectrometry (IM-MS) for metabolomics and lipidomics has facilitated the separation and the identification of metabolites and lipids in compl...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.10.033
更新日期：2018-02-01 00:00:00
abstract：:A number of nitrile-related enzymes have been screened over the past year for use in synthetic applications. There have also been significant advances in our understanding of the structures and modes of regulation of metal-containing nitrile hydratases. Enzyme structural characterization has provided new insights into...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(99)00058-7
更新日期：2000-02-01 00:00:00
abstract：:Major advances have been made in our understanding of cytochrome c oxidase owing to continued crystallographic work on important intermediates. This, together with a wealth of data derived from selective mutations and sophisticated spectroscopic probes, has provided significant new insights into oxidase dioxygen chemi...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(99)80024-6
更新日期：1999-04-01 00:00:00
