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Author

Mark L. Benson

Bio: Mark L. Benson is a academic researcher from University of Michigan. The author has contributed to research in topic(s): Druggability & Binding site. The author has an hindex of 11, co-authored 13 publication(s) receiving 3838 citation(s). Previous affiliations of Mark L. Benson include University of Florida & National Institutes of Health.

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Topics: Druggability, Binding site, Protein ligand ...read more
Papers
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Open accessJournal ArticleDOI: 10.1093/NAR/GKV1222
Melissa J. Landrum1, Jennifer M. Lee1, Mark L. Benson1, Garth Brown1  +15 moreInstitutions (1)
Abstract: ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/) at the National Center for Biotechnology Information (NCBI) is a freely available archive for interpretations of clinical significance of variants for reported conditions. The database includes germline and somatic variants of any size, type or genomic location. Interpretations are submitted by clinical testing laboratories, research laboratories, locus-specific databases, OMIM®, GeneReviews™, UniProt, expert panels and practice guidelines. In NCBI's Variation submission portal, submitters upload batch submissions or use the Submission Wizard for single submissions. Each submitted interpretation is assigned an accession number prefixed with SCV. ClinVar staff review validation reports with data types such as HGVS (Human Genome Variation Society) expressions; however, clinical significance is reported directly from submitters. Interpretations are aggregated by variant-condition combination and assigned an accession number prefixed with RCV. Clinical significance is calculated for the aggregate record, indicating consensus or conflict in the submitted interpretations. ClinVar uses data standards, such as HGVS nomenclature for variants and MedGen identifiers for conditions. The data are available on the web as variant-specific views; the entire data set can be downloaded via ftp. Programmatic access for ClinVar records is available through NCBI's E-utilities. Future development includes providing a variant-centric XML archive and a web page for details of SCV submissions.

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1,680 Citations


Open accessJournal ArticleDOI: 10.1093/NAR/GKX1153
Melissa J. Landrum1, Jennifer M. Lee1, Mark L. Benson1, Garth Brown1  +18 moreInstitutions (1)
Abstract: ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/) is a freely available, public archive of human genetic variants and interpretations of their significance to disease, maintained at the National Institutes of Health. Interpretations of the clinical significance of variants are submitted by clinical testing laboratories, research laboratories, expert panels and other groups. ClinVar aggregates data by variant-disease pairs, and by variant (or set of variants). Data aggregated by variant are accessible on the website, in an improved set of variant call format files and as a new comprehensive XML report. ClinVar recently started accepting submissions that are focused primarily on providing phenotypic information for individuals who have had genetic testing. Submissions may come from clinical providers providing their own interpretation of the variant ('provider interpretation') or from groups such as patient registries that primarily provide phenotypic information from patients ('phenotyping only'). ClinVar continues to make improvements to its search and retrieval functions. Several new fields are now indexed for more precise searching, and filters allow the user to narrow down a large set of search results.

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Topics: Variant Call Format (53%)

1,264 Citations


Open accessJournal ArticleDOI: 10.1023/A:1016357510143
01 Jan 2001-
Abstract: The vascular smooth muscle cell plays a significant role in many important cardiovascular disorders, and smooth muscle biology is therefore important to cardiovascular research. The mouse is critical to basic cardiovascular research, largely because techniques for genetic manipulation are more fully developed in the mouse than in any other mammalian species. We describe here a technique for isolating smooth muscle cells from a single mouse aorta. This technique is particularly useful when material is limiting, as is frequently the case when genetically modified animals are being characterized.

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Topics: Vascular smooth muscle (67%), Myocyte (59%)

241 Citations


Open accessJournal ArticleDOI: 10.1002/PROT.20512
Liegi Hu1, Mark L. Benson1, Richard D. Smith1, Michael G. Lerner1  +1 moreInstitutions (1)
15 Aug 2005-Proteins
Abstract: Binding MOAD (Mother of All Data- bases) is the largest collection of high-quality, protein- ligand complexes available from the Protein Data Bank. At this time, Binding MOAD contains 5331 protein-ligand complexes comprised of 1780 unique protein families and 2630 unique ligands. We have searched the crystallography papers for all 5000 structures and compiled binding data for 1375 (26%) of the protein-ligand complexes. The binding-affinity data ranges 13 orders of magnitude. This is the largest collection of binding data reported to date in the literature. We have also addressed the issue of redun- dancy in the data. To create a nonredundant dataset, one protein from each of the 1780 protein families was chosen as a representative. Representatives were cho- sen by tightest binding, best resolution, etc. For the 1780 "best" complexes that comprise the nonredun- dant version of Binding MOAD, 475 (27%) have bind- ing data. This significant collection of protein-ligand complexes will be very useful in elucidating the bio- physical patterns of molecular recognition and enzy- matic regulation. The complexes with binding-affinity data will help in the development of improved scoring functions and structure-based drug discovery tech- niques. The dataset can be accessed at http://www. BindingMOAD.org. Proteins 2005;60:333-340.

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Topics: Protein Data Bank (51%)

216 Citations


Open accessJournal ArticleDOI: 10.1093/NAR/GKM911
Abstract: Binding MOAD (Mother of All Databases) is a database of 9836 protein–ligand crystal structures. All biologically relevant ligands are annotated, and experimental binding-affinity data is reported when available. Binding MOAD has almost doubled in size since it was originally introduced in 2004, demonstrating steady growth with each annual update. Several technologies, such as natural language processing, help drive this constant expansion. Along with increasing data, Binding MOAD has improved usability. The website now showcases a faster, more featured viewer to examine the protein–ligand structures. Ligands have additional chemical data, allowing for cheminformatics mining. Lastly, logins are no longer necessary, and Binding MOAD is freely available to all at http://www.BindingMOAD.org.

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131 Citations


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Open accessJournal ArticleDOI: 10.1093/NAR/GKR777
Anna Gaulton1, Louisa J. Bellis1, A. Patrícia Bento1, Jon Chambers1  +7 moreInstitutions (1)
Abstract: ChEMBL is an Open Data database containing binding, functional and ADMET information for a large number of drug-like bioactive compounds. These data are manually abstracted from the primary published literature on a regular basis, then further curated and standardized to maximize their quality and utility across a wide range of chemical biology and drug-discovery research problems. Currently, the database contains 5.4 million bioactivity measurements for more than 1 million compounds and 5200 protein targets. Access is available through a web-based interface, data downloads and web services at: https://www.ebi.ac.uk/chembldb.

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Topics: chEMBL (62%)

2,476 Citations


Open accessJournal ArticleDOI: 10.1038/NATURE17946
Alexis C. Komor1, Yongjoo Kim2, Yongjoo Kim1, Michael S. Packer2  +5 moreInstitutions (2)
19 May 2016-Nature
Abstract: Current genome-editing technologies introduce double-stranded (ds) DNA breaks at a target locus as the first step to gene correction. Although most genetic diseases arise from point mutations, current approaches to point mutation correction are inefficient and typically induce an abundance of random insertions and deletions (indels) at the target locus resulting from the cellular response to dsDNA breaks. Here we report the development of 'base editing', a new approach to genome editing that enables the direct, irreversible conversion of one target DNA base into another in a programmable manner, without requiring dsDNA backbone cleavage or a donor template. We engineered fusions of CRISPR/Cas9 and a cytidine deaminase enzyme that retain the ability to be programmed with a guide RNA, do not induce dsDNA breaks, and mediate the direct conversion of cytidine to uridine, thereby effecting a C→T (or G→A) substitution. The resulting 'base editors' convert cytidines within a window of approximately five nucleotides, and can efficiently correct a variety of point mutations relevant to human disease. In four transformed human and murine cell lines, second- and third-generation base editors that fuse uracil glycosylase inhibitor, and that use a Cas9 nickase targeting the non-edited strand, manipulate the cellular DNA repair response to favour desired base-editing outcomes, resulting in permanent correction of ~15-75% of total cellular DNA with minimal (typically ≤1%) indel formation. Base editing expands the scope and efficiency of genome editing of point mutations.

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Topics: Genome editing (56%), DNA repair (55%), Point mutation (55%) ...read more

2,245 Citations


Open accessJournal ArticleDOI: 10.1038/S41467-018-04768-7
Zhen Liu1, Zongyang Lu2, Guang Yang2, Shisheng Huang2  +10 moreInstitutions (2)
Abstract: A recently developed adenine base editor (ABE) efficiently converts A to G and is potentially useful for clinical applications. However, its precision and efficiency in vivo remains to be addressed. Here we achieve A-to-G conversion in vivo at frequencies up to 100% by microinjection of ABE mRNA together with sgRNAs. We then generate mouse models harboring clinically relevant mutations at Ar and Hoxd13, which recapitulates respective clinical defects. Furthermore, we achieve both C-to-T and A-to-G base editing by using a combination of ABE and SaBE3, thus creating mouse model harboring multiple mutations. We also demonstrate the specificity of ABE by deep sequencing and whole-genome sequencing (WGS). Taken together, ABE is highly efficient and precise in vivo, making it feasible to model and potentially cure relevant genetic diseases. CRISPR-based base editors allow for single nucleotide genome editing in a range of organisms. Here the authors demonstrate the in vivo generation of mouse models carrying clinically relevant mutations using C→T and A→G editors.

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Topics: Genome editing (52%)

2,094 Citations


Journal ArticleDOI: 10.1038/NATURE06526
12 Dec 2007-Nature
Abstract: Targeting the interfaces between proteins has huge therapeutic potential, but discovering small-molecule drugs that disrupt protein-protein interactions is an enormous challenge. Several recent success stories, however, indicate that protein-protein interfaces might be more tractable than has been thought. These studies discovered small molecules that bind with drug-like potencies to 'hotspots' on the contact surfaces involved in protein-protein interactions. Remarkably, these small molecules bind deeper within the contact surface of the target protein, and bind with much higher efficiencies, than do the contact atoms of the natural protein partner. Some of these small molecules are now making their way through clinical trials, so this high-hanging fruit might not be far out of reach.

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1,688 Citations


Journal ArticleDOI: 10.1126/SCIENCE.1208351
28 Oct 2011-Science
Abstract: An outstanding challenge in the field of molecular biology has been to understand the process by which proteins fold into their characteristic three-dimensional structures. Here, we report the results of atomic-level molecular dynamics simulations, over periods ranging between 100 μs and 1 ms, that reveal a set of common principles underlying the folding of 12 structurally diverse proteins. In simulations conducted with a single physics-based energy function, the proteins, representing all three major structural classes, spontaneously and repeatedly fold to their experimentally determined native structures. Early in the folding process, the protein backbone adopts a nativelike topology while certain secondary structure elements and a small number of nonlocal contacts form. In most cases, folding follows a single dominant route in which elements of the native structure appear in an order highly correlated with their propensity to form in the unfolded state.

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Topics: Contact order (65%), Protein folding (57%), Protein structure (54%) ...read more

1,483 Citations


Performance
Metrics

Author's H-index: 11

No. of papers from the Author in previous years
YearPapers
20191
20181
20171
20161
20121
20112

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Author's top 5 most impactful journals

Nucleic Acids Research

3 papers, 3K citations

Proteins

1 papers, 216 citations

Journal of Medicinal Chemistry

1 papers, 26 citations

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