Abstract：
:To promote more productive combinatorial endeavors, the Diversity Space methodology introduced here enables similarity comparisons at the library level. Particularly at an early screening stage, when little or no information is available regarding the pharmacophoric entities necessary for binding, it is more efficient to select or discard an entire ensemble of molecules at once, rather than focus on individual compounds. Also described are applications of the methodology to a form of scaffold hopping, herein categorized as "soft" scaffold hopping, and to a newly introduced approach called surrogate synthesis, both of which are furthered by library-level information that is absent in more traditional molecular similarity calculations.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Fitzgerald SH,Sabat M,Geysen HMdoi
10.1021/ci060066zsubject
Has Abstractpub_date
2006-07-01 00:00:00pages
1588-97issue
4eissn
1549-9596issn
1549-960Xjournal_volume
46pub_type
杂志文章abstract：:Protein-protein interactions play a key role in a multitude of biological processes, such as signal transduction, de novo drug design, immune responses, and enzymatic activities. It is of great interest to understand how proteins interact with each other. The general approach is to explore all possible poses and ident...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci5002372
更新日期：2014-06-23 00:00:00
abstract：:Voltage-gated sodium channels (VGSC) are attractive targets for drug discovery because of the broad therapeutic potential of their modulators. On the basis of the structure of marine alkaloid clathrodin, we have recently discovered novel subtype-selective VGSC modulators I and II that were used as starting points for ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400505e
更新日期：2013-12-23 00:00:00
abstract：:Human telomeric DNA G-quadruplex has been identified as a good therapeutic target in cancer treatment. G-quadruplex-specific ligands that stabilize the G-quadruplex have great potential to be developed as anticancer agents. Two crystal structures (an apo form of parallel stranded human telomeric G-quadruplex and its h...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00287
更新日期：2017-11-27 00:00:00
abstract：:In the preceding paper (Duca, J. S.; Madison, V. S.; Voigt, J. H. J. Chem. Inf. Model. 2008, 48, 659-668), the accuracy of docking and affinity predictions of the Gold and Glide programs were investigated using single protein conformations spanning 150 CDK2/inhibitor crystallographic complexes. High docking accuracy w...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700428d
更新日期：2008-03-01 00:00:00
abstract：:A new variable selection wrapper method named the Monte Carlo variable selection (MCVS) method was developed utilizing the framework of the Monte Carlo cross-validation (MCCV) approach. The MCVS method reports the variable selection results in the most conventional and common measure of statistical hypothesis testing,...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700283s
更新日期：2008-02-01 00:00:00
abstract：:With the hope of discovering effective analgesics with fewer side effects, attention has recently shifted to allosteric modulators of the opioid receptors. In the past two years, the first chemotypes of positive or silent allosteric modulators (PAMs or SAMs, respectively) of μ- and δ-opioid receptor types have been re...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00388
更新日期：2015-09-28 00:00:00
abstract：:Central to Hsp90's biological function is its ability to interconvert between various conformational states. Drug targeting of Hsp90's regulatory mechanisms, including its modulation by cochaperone association, presents as an attractive therapeutic strategy for Hsp90 associated pathologies. In this study, we utilized ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00630
更新日期：2018-02-26 00:00:00
abstract：:In this article, we present a systematic way to classify a family of high-genus fullerenes (HGFs) by decomposing them into two types of necklike structures, which are the negatively curved parts of parent toroidal carbon nanotubes. By replacing the faces of a uniform polyhedron with these necks, an HGF polyhedron corr...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci9001124
更新日期：2009-07-01 00:00:00
abstract：:It is demonstrated that the fragmentation of druglike molecules by applying simplistic pseudo-retrosynthesis results in a stock of chemically meaningful building blocks for de novo molecule generation. A stochastic search algorithm in conjunction with ligand-based similarity scoring (Flux: fragment-based ligand builde...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci0503560
更新日期：2006-03-01 00:00:00
abstract：:Due to the recent availability of high quality small molecule databases, such as ZINC and PubChem,1,2 virtual screening is playing an even more important role in identifying biologically relevant molecules in drug discovery campaigns. The success of pharmacophore-based virtual screening (PBVS) relies largely on the ac...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700089w
更新日期：2007-07-01 00:00:00
abstract：:We describe a novel deep learning neural network method and its application to impute assay pIC50 values. Unlike conventional machine learning approaches, this method is trained on sparse bioactivity data as input, typical of that found in public and commercial databases, enabling it to learn directly from correlation...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00768
更新日期：2019-03-25 00:00:00
abstract：:The Common Instrument Middleware Architecture (CIMA) aims at Grid-enabling a wide range of scientific instruments and sensors to enable easy access to and sharing and storage of data produced by these instruments and sensors. This paper describes the implementation of CIMA applied to the field of single-crystal X-ray ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050368l
更新日期：2006-05-01 00:00:00
abstract：:DNA damage alters genetic information and adversely affects gene expression pathways leading to various complex genetic disorders and cancers. DNA repair proteins recognize and rectify DNA damage and mismatches with high fidelity. A critical molecular event that occurs during most protein-mediated DNA repair processes...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00636
更新日期：2018-03-26 00:00:00
abstract：:Scoring the activity of compounds in phenotypic high-throughput assays presents a unique challenge because of the limited resolution and inherent measurement error of these assays. Techniques that leverage the structural similarity of compounds within an assay can be used to improve the hit-recovery rate from screenin...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050087d
更新日期：2005-11-01 00:00:00
abstract：:With continually increased computer power, molecular mechanics force field-based approaches, such as the endpoint methods of molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) and molecular mechanics generalized Born surface area (MM-GBSA), have been routinely applied in both drug lead identification and opt...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00934
更新日期：2020-12-28 00:00:00
abstract：:SIRT2, which is a NAD+ (nicotinamide adenine dinucleotide) dependent deacetylase, has been demonstrated to play an important role in the occurrence and development of a variety of diseases such as cancer, ischemia-reperfusion, and neurodegenerative diseases. Small molecule inhibitors of SIRT2 are thought to be potenti...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00714
更新日期：2017-04-24 00:00:00
abstract：:G-protein-coupled receptors (GPCRs) transmit signals into the cell in response to ligand binding at its extracellular domain, which is characterized by the coupling of agonist-induced receptor conformational change to guanine nucleotide (GDP) exchange with guanosine triphosphate on a heterotrimeric (αβγ) guanine nucle...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00432
更新日期：2020-08-24 00:00:00
abstract：:We used synthetic peloruside A for the commercial preparation of [³H]peloruside A. The radiolabeled compound bound to preformed tubulin polymer in amounts stoichiometric with the polymer's tubulin content, with an apparent K(d) value of 0.35 μM. A less active peloruside A analogue, (11-R)-peloruside A and laulimalide ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci1002894
更新日期：2010-11-22 00:00:00
abstract：:One tactic for cysteine protease inhibition is to form a covalent bond between an electrophilic atom of the inhibitor and the thiol of the catalytic cysteine. In this study, we evaluate the reaction free energy obtained from a hybrid quantum mechanical/molecular mechanical (QM/MM) free energy profile as a predictor of...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00847
更新日期：2020-02-24 00:00:00
abstract：:The prediction of protein-ligand binding affinity has recently been improved remarkably by machine-learning-based scoring functions. For example, using a set of simple descriptors representing the atomic distance counts, the RF-Score improves the Pearson correlation coefficient to about 0.8 on the core set of the PDBb...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00049
更新日期：2017-04-24 00:00:00
abstract：:FFAR4 has been considered as a potential target for metabolic diseases, including diabetes. Some compounds with biphenyl scaffold, represented by compound SR13 reported by our group, showed significant FFAR4 selectivity. However, the molecular basis for their selectivity has not been definitely disclosed. This study p...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00735
更新日期：2019-10-28 00:00:00
abstract：:Covalent inhibitors have been gaining increased attention in drug discovery due to their beneficial properties such as long residence time, high biochemical efficiency, and specificity. Optimization of covalent inhibitors is a complex task that involves parallel monitoring of the noncovalent recognition elements and t...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00834
更新日期：2020-12-28 00:00:00
abstract：:Protein-polysaccharide complexes constructed via self-assembly methods are often used to develop novel biomaterials for a wide range of applications in biomedicine, food, and biotechnology. The objective of this work was to investigate theoretically and to demonstrate via constant-pH Monte Carlo simulations that the c...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00814
更新日期：2020-02-24 00:00:00
abstract：:Big data is one of the key transformative factors which increasingly influences all aspects of modern life. Although this transformation brings vast opportunities it also generates novel challenges, not the least of which is organizing and searching this data deluge. The field of medicinal chemistry is not different: ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00249
更新日期：2017-08-28 00:00:00
abstract：:Side-chain modeling is critical for protein structure prediction since the uniqueness of the protein structure is largely determined by its side-chain packing conformation. In this paper, differing from most approaches that rely on rotamer library sampling, we first propose a novel side-chain rotamer prediction method...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00951
更新日期：2020-12-28 00:00:00
abstract：:The emergence of a large amount of pharmacological, genomic, and network knowledge data provides new challenges and opportunities for drug discovery and development. Identification of real small-molecule drug (SM)-miRNA associations is not only important in the development of effective drug repositioning but also cruc...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00244
更新日期：2020-08-24 00:00:00
abstract：:We present our newly developed and highly efficient lossless compression algorithm for trajectories of atom positions and volumetric data. The algorithm is designed as a two-step approach. In the first step, efficient polynomial extrapolation schemes reduce the information entropy of the data by exploiting both spatia...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00501
更新日期：2018-10-22 00:00:00
abstract：:Water is the natural medium of molecules in the cell and plays an important role in protein structure, function and interaction with small molecule ligands. However, the widely used molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) method for binding energy calculation does not explicitly take account of wa...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci4001794
更新日期：2014-02-24 00:00:00
abstract：:A major concern of chemogenomics is to associate drug activity with biological variables. Several reports have clustered cell line drug activity profiles as well as drug activity-gene expression correlation profiles and noted that the resulting groupings differ but still reflect mechanism of action. The present paper ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci060073n
更新日期：2007-01-01 00:00:00
abstract：:To discover non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) that are effective against both wild-type (WT) virus and variants that encode the clinically troublesome Tyr181Cys (Y181C) RT mutation, virtual screening by docking was carried out using three RT structures and more than 2 million commercial...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci900068k
更新日期：2009-05-01 00:00:00
