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Concepts and Core Principles of Fragment-Based Drug Design

Philine Kirsch, Alwin M Hartman, Anna K H Hirsch, Martin Empting
2019 Molecules  
In this review, a general introduction to fragment-based drug design and the underlying concepts is given.  ...  Building upon the foundation of fragment-based drug discovery (FBDD) and its methodologies, we also highlight a few new trends in FBDD.  ...  Typically, FBDD starts with a screening of a small library of low molecular weight compounds for binding to a particular target. The key advantage of fragments is their low degree of complexity.  ... 
doi:10.3390/molecules24234309 pmid:31779114 pmcid:PMC6930586 fatcat:lj4g7ya5e5hipddcl6j2h22xi4

Advances in diversity profiling and combinatorial series design [chapter]

Dimitris K. Agrafiotis, James C. Myslik, F. Raymond Salemme
1999 Annual Reports in Combinatorial Chemistry and Molecular Diversity  
, using molecular diversity as a means to design and prioritize experiments.  ...  This paper reviews some of the most important computational work in the field of diversity profiling and combinatorial library design, with particular emphasis on methodology and applications.  ...  Most work to date has focused on lead generation, using molecular diversity as a means to design and prioritize experiments.  ... 
doi:10.1007/978-94-017-0735-0_9 fatcat:gyw3bjjowracte76rdbnaor5hi

Natural product drug discovery in the artificial intelligence era

Fernanda I Saldivar-Gonzalez, Victor Daniel Aldas-Bulos, José Luis Medina-Franco, Fabien Plisson
2022 Chemical Science  
Their unique characteristics and structural diversity continue to marvel scientists for developing NP-inspired medicines, even...  ...  Beyond its application to identify life in outer space, one might divert the original purpose of the molecular complexity index as a fitness function to optimize the design of NPinspired drugs.  ...  They concluded that the NPs (complete compounds and fragments) largely delineated the chemical space. 191 Of note, fragment libraries of NPs can be very useful for the rational fragment-based design of  ... 
doi:10.1039/d1sc04471k pmid:35282622 pmcid:PMC8827052 fatcat:jyfupubc2bgb7p4v6b62apgtfq

Bioactive Compound Collections: From Design to Target Identification

Luca Laraia, Lucas Robke, Herbert Waldmann
2018 Chem  
We highlight efficient ways to screen the resulting libraries in order to maximize hit rates and the chance of discovering new modes of action.  ...  Therefore, attention has turned to increasing the biological relevance of the compounds to be used in chemical biology and medicinal chemistry research, as well as maximizing their diversity within this  ...  L.L. is grateful to the Alexander von Humboldt Foundation for a fellowship. L.R. is grateful to the Boehringer Ingelheim Fonds for a fellowship.  ... 
doi:10.1016/j.chempr.2018.01.012 fatcat:gon7we3norcrpou6476d62hc5a

Innovative omics-based approaches for prioritisation and targeted isolation of natural products – new strategies for drug discovery

Jean-Luc Wolfender, Marc Litaudon, David Touboul, Emerson Ferreira Queiroz
2019 Natural product reports (Print)  
This review focuses on innovative omics approaches related to the prioritisation of natural extracts, to selection of efficient producing strains and to the targeted isolation of their bioactive constituents  ...  One of the world's largest and most diverse screening libraries of CNEs was developed in the 1980s and 1990s by the National Cancer Institute (NCI).  ...  for molecular formula assignment, on the comparison of fragmentation MS/MS spectra against databases (DBs) and on the visualisation of groupings of these spectra into a molecular network (MN). 29 In  ... 
doi:10.1039/c9np00004f pmid:31073562 fatcat:csamzgmufbagvmjqk334pvg7b4

DEEPGENTM—A Novel Variant Calling Assay for Low Frequency Variants

Bernd Timo Hermann, Sebastian Pfeil, Nicole Groenke, Samuel Schaible, Robert Kunze, Frédéric Ris, Monika Elisabeth Hagen, Johannes Bhakdi
2021 Genes  
A superior sensitivity was also confirmed by orthogonal comparison to a commercially available liquid biopsy-based assay for cancer detection.  ...  Detection of genetic variants in clinically relevant genomic hot-spot regions has become a promising application of next-generation sequencing technology in precision oncology.  ...  We thank Carlo Anacta for his expertise and support in graphic design.  ... 
doi:10.3390/genes12040507 pmid:33808158 fatcat:hktsalsp25c5dg64unihmmoer4

Overcoming Chemical, Biological, and Computational Challenges in the Development of Inhibitors Targeting Protein-Protein Interactions

Luca Laraia, Grahame McKenzie, David R. Spring, Ashok R. Venkitaraman, David J. Huggins
2015 Chemistry and Biology  
From target validation to small-molecule screening and lead optimization, identifying therapeutically relevant PPIs that can be successfully modulated by small molecules is not a simple task.  ...  We conclude by providing a perspective on the field and outlining four innovations that we see as key enabling steps for successful development of small-molecule inhibitors targeting PPIs.  ...  A validated approach for obtaining diverse screening collections is diversity-oriented synthesis (Galloway et al., The apo and holo structures were aligned using residues within 5.0 Å of the ligand, and  ... 
doi:10.1016/j.chembiol.2015.04.019 pmid:26091166 pmcid:PMC4518475 fatcat:5jqgp7z36fdn7ant6p5wmplewe

QuBiLS-MAS, open source multi-platform software for atom- and bond-based topological (2D) and chiral (2.5D) algebraic molecular descriptors computations

José R. Valdés-Martiní, Yovani Marrero-Ponce, César R. García-Jacas, Karina Martinez-Mayorga, Stephen J. Barigye, Yasser Silveira Vaz d'Almeida, Hai Pham-The, Facundo Pérez-Giménez, Carlos A. Morell
2017 Journal of Cheminformatics  
Therefore, the QuBiLS-MAS approach constitutes a useful tool for the diversity analysis of chemical compound datasets and high-throughput screening of structure-activity data.  ...  ; (c) six additional atomic properties to be used as weighting schemes in the calculation of the molecular vectors; (d) four new local-fragments to consider molecular regions of interest; (e) number of  ...  Availability of data and materials The QuBiLS-MAS software and the respective user manual are freely available online at www.tomocomd.com.  ... 
doi:10.1186/s13321-017-0211-5 pmid:29086120 pmcid:PMC5462671 fatcat:kb336oqlsrhwvjp54tc5k4i5ii

Challenges and advances in computational docking: 2009 in review

Elizabeth Yuriev, Mark Agostino, Paul A. Ramsland
2010 Journal of Molecular Recognition  
This review is strongly focused on docking advances in the context of drug design, specifically in virtual screening and fragment-based drug design. E. YURIEV ET AL.  ...  Any pose above the cutoff (usually, 2 Å ) is considered incorrect, which leads to a loss of potentially useful information,  ...  Fragment-based docking The use of molecular docking to assist in Fragment-Based Drug Design (FBDD) (103,104) is logically obvious.  ... 
doi:10.1002/jmr.1077 pmid:21360606 fatcat:e6wp7hya45hbnh4wfhqeugvcyi

Ligand Electron Density Shape Recognition Using 3D Zernike Descriptors [chapter]

Prasad Gunasekaran, Scott Grandison, Kevin Cowtan, Lora Mak, David M. Lawson, Richard J. Morris
2009 Lecture Notes in Computer Science  
Electron density for a bound ligand is expanded in an orthogonal polynomial series (3D Zernike polynomials) and the coefficients from this expansion are employed to construct rotation-invariant descriptors  ...  We could identify the correct ligand as the first hit in about 30 % of the cases, within the top five in a further 30 % of the cases, and giving rise to an 80 % probability of getting the correct ligand  ...  This project was funded in part by a BBSRC Tools and Resources grant -grant number CA340H10B.  ... 
doi:10.1007/978-3-642-04031-3_12 fatcat:cdvh72dqx5cw5dyeeu7gruiyfi

Hampering the early aggregation of PrP-E200K protein by charge-based inhibitors: a computational study

Mariangela Agamennone, Loriano Storchi, Alessandro Marrone, Roberto Paciotti
2021 Journal of Computer-Aided Molecular Design  
These structural data were then employed to drive structure-based virtual screening and fragment-based approaches to the seeking of small molecular binders of the PrP-E200K.  ...  AbstractA multilayered computational workflow was designed to identify a druggable binding site on the surface of the E200K pathogenic mutant of the human prion protein, and to investigate the effect of  ...  Acknowledgements We thank the Ministry of Education, University and Research (MIUR) for financial support. Moreover, we are thankful to Federica Sommonte for her valuable support.  ... 
doi:10.1007/s10822-021-00393-7 pmid:34110550 pmcid:PMC8213589 fatcat:klpqfa2omzgk7gjx5jy2rnxipi

Opportunities in the design and application of RNA for gene expression control

Maureen McKeague, Remus S. Wong, Christina D. Smolke
2016 Nucleic Acids Research  
Researchers have focused on the use of RNA for gene expression control due to its versatility in sensing molecular ligands and the relative ease by which RNA can be modeled and designed compared to proteins  ...  The past decade of synthetic biology research has witnessed numerous advances in the development of tools and frameworks for the design and characterization of biological systems.  ...  While RNA devices have been designed to respond to diverse molecular inputs, for the purposes of this perspective we will focus on protein and small molecule-based inputs, as devices responsive to RNA-based  ... 
doi:10.1093/nar/gkw151 pmid:26969733 pmcid:PMC4838379 fatcat:zbzcyarihjafzbuw2o5f7i45km

Omics-Based Strategies in Precision Medicine: Toward a Paradigm Shift in Inborn Errors of Metabolism Investigations

Abdellah Tebani, Carlos Afonso, Stéphane Marret, Soumeya Bekri
2016 International Journal of Molecular Sciences  
Perspectives regarding the use of multi-omics approaches for inborn errors of metabolism (IEM) are presented by introducing a new paradigm shift in addressing IEM investigations in the post-genomic era  ...  In this review, we present state-of-the-art multi-omics data analysis strategies in a clinical context. The challenges of omics-based biomarker translation are discussed.  ...  Acknowledgments: This work was supported by Normandy University, the Institut National de la Santé et de la Recherche Médicale (INSERM), the Conseil Régional de Normandie, Labex SynOrg (ANR-11-LABX-0029), and  ... 
doi:10.3390/ijms17091555 pmid:27649151 pmcid:PMC5037827 fatcat:426cvphidjgd3mtta76lcdoj7q

QSAR without borders

Eugene N. Muratov, Jürgen Bajorath, Robert P. Sheridan, Igor V. Tetko, Dmitry Filimonov, Vladimir Poroikov, Tudor I. Oprea, Igor I. Baskin, Alexandre Varnek, Adrian Roitberg, Olexandr Isayev, Stefano Curtalolo (+7 others)
2020 Chemical Society Reviews  
Word cloud summary of diverse topics associated with QSAR modeling that are discussed in this review.  ...  It is often used as an important filter for screening virtual libraries and in de novo design studies.  ...  of high-throughput screening technologies and proliferation of diverse assays have enabled screening of a larger number of molecules in more diverse assays.  ... 
doi:10.1039/d0cs00098a pmid:32356548 fatcat:l456rjoqbzgehkqa63uvqrv2gy

Mathematical models of protease-based enzymatic biosensors [article]

Deepak K. Agrawal, Sagar Khare, Eduardo D Sontag
2019 bioRxiv   pre-print
These fast protease-based biosensors can be used to implement complex molecular circuits with a capability of processing multiple inputs controllably and algorithmically.  ...  These multiple steps together require up to several hours to respond to a single stimulus, and this limits the overall speed and complexity of genetic circuits.  ...  Acknowledgement This research was supported in part by grants DARPA FA8650-18-1-7800 and NSF 1817936.  ... 
doi:10.1101/695320 fatcat:i7k4fxp4x5cstais2lp55fxasu
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