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Structures and disulfide cross-linking of de novo designed therapeutic mini-proteins

Daniel-Adriano Silva, Lance Stewart, Kwok-Ho Lam, Rongsheng Jin, David Baker
2018 The FEBS Journal  
Recent advances in computational protein design now enable the massively parallel de novo design and experimental characterization of small hyperstable binding proteins with potential therapeutic activity  ...  De novo miniprotein design and stabilization D.-A. Silva et al.  ...  Acknowledgements D-AS thanks MJ Countryman for help editing this manuscript. D-AS acknowledges support from the PEW Latin-American Fellowship in the biomedical sciences and Mexico's CONACyT.  ... 
doi:10.1111/febs.14394 pmid:29389072 pmcid:PMC6001749 fatcat:sypsjomfmncgnl6jiare3bomji

Large-scale integrated super-computing platform for next generation virtual drug discovery

Wayne Mitchell, Shunji Matsumoto
2011 Current Opinion in Chemical Biology  
A specific embodiment of the technology, integrating de novo, abstract fragment based drug design, sophisticated molecular simulation, and the ability to calculate thermodynamic binding constants with  ...  Traditional drug discovery starts by experimentally screening chemical libraries to find hit compounds that bind to protein targets, modulating their activity.  ...  WM thanks the Institute of High Performance Computing and the A*STAR Computational Resource Centre for their support in advancing computational molecular design in Singapore.  ... 
doi:10.1016/j.cbpa.2011.06.005 pmid:21723773 pmcid:PMC7108376 fatcat:kel7f5qt2ncz3bwodglu3gk4ne

Hierarchical design of artificial proteins and complexes toward synthetic structural biology

Ryoichi Arai
2017 Biophysical Reviews  
design/creation of artificial proteins and complexes, novel protein folds, ideal/optimized protein structures, novel binding proteins for targeted therapeutics, and selfassembling nanomaterials.  ...  novo proteins, protein nanobuilding block strategy for constructing nano-architectures, protein-metal-organic frameworks for 3D protein complex crystals, and rational and computational approaches for  ...  More recently, global analysis of protein folding ) and massively parallel design of de novo binding proteins for targeted therapeutics were reported by Baker and colleagues.  ... 
doi:10.1007/s12551-017-0376-1 pmid:29243094 pmcid:PMC5899735 fatcat:k724ocy7knaxtjbklk5dwmfedu

Approaches to the Structure-Based Design of Antivirulence Drugs: Therapeutics for the Post-Antibiotic Era

Nolan Neville, Zongchao Jia
2019 Molecules  
The growing number of validated virulence protein targets for which structural information has been obtained, along with advances in computational power and screening algorithms, make the rational design  ...  Here, we review the principles of structure-based drug design and the exciting opportunities this technique presents for antivirulence drug discovery.  ...  Acknowledgments: We thank NSERC and Queen's University for funding support to the Jia lab. Conflicts of Interest: The authors declare that there are no conflicts of interest.  ... 
doi:10.3390/molecules24030378 fatcat:htb5eotfkvgyzlzb53qojp755m

Identification of DCAF1 by Clinical Exome Sequencing and Methylation Analysis as a Candidate Gene for Autism and Intellectual Disability: A Case Report

Jeffery L. Clothier, Amy N. Grooms, Patricia A. Porter-Gill, Pritmohinder S. Gill, G. Bradley Schaefer
2022 Journal of Personalized Medicine  
Taken together, this suggests that the de novo DCAF1 variant may be a newly identified molecular cause of autism and intellectual disability.  ...  He was referred as an adult to our neurodiversity clinic and a full exome trio sequencing with reflex to mitochondrial genes identified a de novo variant of uncertain significance in a candidate gene,  ...  The funders had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.  ... 
doi:10.3390/jpm12060886 pmid:35743672 pmcid:PMC9224943 fatcat:vyajcpzexrh53f2fb2zurcawhe

Designing Short Peptides to Block the Interaction of SARS-CoV-2 and Human ACE2 for COVID-19 Therapeutics

Abdul Basit, Asad Mustafa Karim, Muhammad Asif, Tanveer Ali, Jung Hun Lee, Jeong Ho Jeon, Shafiq ur Rehman, Sang Hee Lee
2021 Frontiers in Pharmacology  
We suggest that blocking the RBD through de novo designed peptides can serve as a potential candidate for COVID-19 treatment after further clinical investigations.  ...  Thus, these can block all the binding residues required for binding to cell surface receptor. We used selected amino acid regions (21–40 and 65–75) of ACE2 as scaffold for the de novo peptide design.  ...  Massively Parallel De Novo Protein Design for Targeted Therapeutics.  ... 
doi:10.3389/fphar.2021.731828 pmid:34512357 pmcid:PMC8430035 fatcat:ymif76k5zjdujg7x7mokhmmmry

Protein folding and de novo protein design for biotechnological applications

George A. Khoury, James Smadbeck, Chris A. Kieslich, Christodoulos A. Floudas
2014 Trends in Biotechnology  
Despite challenges in protein folding, de novo protein design has recently demonstrated significant success via computational techniques.  ...  We review advances and challenges in protein structure prediction and de novo protein design, and highlight their interplay in successful biotechnological applications.  ...  Figure 1 schematically shows the roadmap and key challenges in protein structure prediction and de novo protein design.  ... 
doi:10.1016/j.tibtech.2013.10.008 pmid:24268901 pmcid:PMC3922204 fatcat:a5eqtqkb7zcgpgxqjyxhz5llpu

Massively parallel reporter assays discover de novo exonic splicing mutants in paralogs of Autism genes

Christy L. Rhine, Christopher Neil, Jing Wang, Samantha Maguire, Luke Buerer, Mitchell Salomon, Ijeoma C. Meremikwu, Juliana Kim, Natasha T. Strande, William G. Fairbrother, Gregory M. Cooper
2022 PLoS Genetics  
and identified 42 exonic splicing mutants out of 725 coding de novo variants discovered in the sequencing of ASD families.  ...  To determine the contribution of defective splicing in Autism Spectrum Disorders (ASD), the most common neurodevelopmental disorder, a high throughput Massively Parallel Splicing Assay (MaPSY) was employed  ...  to discover de novo variants that increase risk for developing autism.  ... 
doi:10.1371/journal.pgen.1009884 pmid:35051175 pmcid:PMC8775188 fatcat:rb4kdntupzactl7wo76cg63igi

Diagnostic approach for genetic causes of intellectual disability

Shin-Young Yim
2015 Journal of Genetic Medicine  
The advent of technologies such as array comparative genomic hybridization, single nucleotide polymorphism genotyping arrays, and massively parallel sequencing has shown that de novo copy number variations  ...  for personalized therapy when it becomes available in the near future.  ...  The advent of technologies such as array CGH, SNP genotyping arrays, and massively parallel sequencing has shown that de novo CNVs and single nucleotide variations affecting the coding region are major  ... 
doi:10.5734/jgm.2015.12.1.6 fatcat:p544v5ka2nakrn5yitqzrf34r4

The Use of Next-Generation Sequencing for Research and Diagnostics for Intellectual Disability

Ricardo Harripaul, Abdul Noor, Muhammad Ayub, John B. Vincent
2017 Cold Spring Harbor Perspectives in Medicine  
Fortunately for researchers and diagnosticians alike, the recent advent of massively parallel sequencing technologies, or next-generation sequencing (NGS) has made an apparently impossible task tractable  ...  A recent review estimates in excess of 2500 genes for ID.  ...  Huang et al. (2012) used targeted massively paralleled sequencing to identify a noncoding, regulatory variant in the known ID gene HCFC1.  ... 
doi:10.1101/cshperspect.a026864 pmid:28250017 fatcat:p2eoimmomrcybebjwjmddflb4i

Dissecting Therapeutic Resistance to RAF Inhibition in Melanoma by Tumor Genomic Profiling

Nikhil Wagle, Caroline Emery, Michael F. Berger, Matthew J. Davis, Allison Sawyer, Panisa Pochanard, Sarah M. Kehoe, Cory M. Johannessen, Laura E. MacConaill, William C. Hahn, Matthew Meyerson, Levi A. Garraway
2011 Journal of Clinical Oncology  
for sequencing by massively parallel sequencing in the PLX4032-resistant sample.  ...   Discussion Using targeted, massively parallel sequencing, we identified an activating MEK1 mutation in a patient who developed resistance to a selective RAF inhibitor.  ... 
doi:10.1200/jco.2010.33.2312 pmid:21383288 pmcid:PMC3157968 fatcat:jsrajnf43naajlvlrrxpfql4zi

Current Perspectives in Autism Spectrum Disorder: From Genes to Therapy

Maria Chahrour, Brian J. O'Roak, Emanuela Santini, Rodney C. Samaco, Robin J. Kleiman, M. Chiara Manzini
2016 Journal of Neuroscience  
The complex genetics of ASD Recent advances, including genome-wide copy number arrays, massively parallel sequencing, new analysis paradigms, and innovative cohorts, have begun to unravel the genetic complexity  ...  Starting in 2009, the technology to selectively sequence all of the protein-coding regions (exons) of the genome (i.e., the "exome") became widely avail-  ...  Genes with de novo mutations also show strong enrichment for fragile X mental retardation protein targets, chromatin modifiers (e.g., CHD8, CHD2, ARID1B), embryonically expressed genes (e.g., TBR1, DYRK1A  ... 
doi:10.1523/jneurosci.2335-16.2016 pmid:27911742 pmcid:PMC5125207 fatcat:na6rhuuglvgzri3dqijobh5p5m

De Novo Gene Expression Reconstruction in Space

Je H. Lee
2017 Trends in Molecular Medicine  
needed to efficiently assemble a gene expression atlas de novo.  ...  Here, we discuss potential next-generation approaches for de novo assembly of the transcriptome in space, and propose more efficient methods of detecting long-range spatial variations in gene expression  ...  Acknowledgments We would like to acknowledge the support of NIGMS R35, The V Foundation, STARR Cancer Consortium, Human Scientific Frontier Program, and Pershing Square Foundation, NCI, and Northwell/CSHL for  ... 
doi:10.1016/j.molmed.2017.05.004 pmid:28571832 pmcid:PMC5514424 fatcat:ek2est56qrd5xin63v7jbqhgle

Evolving scenario of big data and Artificial Intelligence (AI) in drug discovery

Manish Kumar Tripathi, Abhigyan Nath, Tej P. Singh, A. S. Ethayathulla, Punit Kaur
2021 Molecular diversity  
novo molecule design and discovery in this big data era.  ...  The accumulation of massive data in the plethora of Cheminformatics databases has made the role of big data and artificial intelligence (AI) indispensable in drug design.  ...  Homology modelling and de novo protein design are the traditional methods for structure modelling.  ... 
doi:10.1007/s11030-021-10256-w pmid:34159484 pmcid:PMC8219515 fatcat:p3lsp57x6rbnxgxdu7y5dggdeu

Circumventing Cancer Drug Resistance in the Era of Personalized Medicine

Levi A. Garraway, Pasi A. Jänne
2012 Cancer Discovery  
In this review, we provide a historical background on drug resistance and a framework for understanding the common ways by which cancers develop resistance to targeted therapies.  ...  Significance: Increased knowledge of drug resistance mechanisms will aid in the development of effective therapies for patients with cancer.  ...  Acknowledgments We thank Judit Jane-Valbuena for help with the figures. Grant Support  ... 
doi:10.1158/ pmid:22585993 fatcat:af46qlmdzzcxtl4mzkvedpljwa
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