Abstract:
:Reaction databases provide a great deal of useful information to assist planning of experiments but do not provide any interpretation or chemical concepts to accompany this information. In this work, reactions are labeled with experimental conditions, and network analysis shows that consistencies within clusters of data points can be leveraged to organize this information. In particular, this analysis shows how particular experimental conditions (specifically solvent) are effective in enabling specific organic reactions (Friedel-Crafts, Aldol addition, Claisen condensation, Diels-Alder, and Wittig), including variations within each reaction class. Network analysis shows data points for reactions tend to break into clusters that depend on the catalyst and chemical structure. This type of clustering, which mimics how a chemist reasons, is derived directly from the network. Therefore, the findings of this work could augment synthesis planning by providing predictions in a fashion that mimics human chemists. To numerically evaluate solvent prediction ability, three methods are compared: network analysis (through the k-nearest neighbor algorithm), a support vector machine, and a deep neural network. The most accurate method in 4 of the 5 test cases is the network analysis, with deep neural networks also showing good prediction scores. The network analysis tool was evaluated by an expert panel of chemists, who generally agreed that the algorithm produced accurate solvent choices while simultaneously being transparent in the underlying reasons for its predictions.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Walker E,Kammeraad J,Goetz J,Robo MT,Tewari A,Zimmerman PMdoi
10.1021/acs.jcim.9b00313subject
Has Abstractpub_date
2019-09-23 00:00:00pages
3645-3654issue
9eissn
1549-9596issn
1549-960Xjournal_volume
59pub_type
杂志文章abstract::Resonance structures of polycyclic aromatic hydrocarbons can be associated with numerical formulas by assigning pi-electrons of C=C double bonds to individual benzenoid rings. Each C=C double bond in a resonance structure assigns two pi-electrons to a ring in a fused-benzenoid system if it is not shared by adjacent ri...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci050196s
更新日期:2006-01-01 00:00:00
abstract::Selecting a small subset of descriptors from a large pool to build a predictive quantitative structure-activity relationship (QSAR) model is an important step in the QSAR modeling process. In general, subset selection is very hard to solve, even approximately, with guaranteed performance bounds. Traditional approaches...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci600563w
更新日期:2007-05-01 00:00:00
abstract::Great attention has been paid to the clinical significance of phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil, tadalafil, and vardenafil widely used for erectile dysfunction. However, sildenafil causes side effects on visual functions since it shows similar potencies to inhibit PDE5 and PDE6, whereas tadalaf...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400458z
更新日期:2013-11-25 00:00:00
abstract::Group 1 metabotropic glutamate receptors (mGluR) are G-protein coupled receptors with a large bilobate extracellular ligand binding region (LBR) that resembles a Venus fly trap. Closing of this LBR in the presence of a ligand is associated with the activation of the receptor. From conformational sampling of the LBR-li...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400160x
更新日期:2013-06-24 00:00:00
abstract::Small molecule flexible alignment is a critical component of both ligand- and structure-based methods in computer-aided drug discovery. Despite its importance, the availability of high-quality flexible alignment software packages is limited. Here, we present BCL::MolAlign, a freely available property-based molecular a...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00020
更新日期:2019-02-25 00:00:00
abstract::As a key player in cell adhesion, the glycoprotein fibronectin is involved in the complex mechanobiology of the extracellular matrix. Although the function of many modules in the fibronectin molecule has already been understood, the structure and biological relevance of the C-terminal cross-linked region (CTXL) still ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00555
更新日期:2019-10-28 00:00:00
abstract::The viral NS5B RNA-dependent RNA-polymerase (RdRp) is one of the best-studied and promising targets for the development of novel therapeutics against hepatitis C virus (HCV). Allosteric inhibition of this enzyme has emerged as a viable strategy toward blocking replication of viral RNA in cell based systems. Herein, we...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci9004749
更新日期:2010-04-26 00:00:00
abstract::Development of coarse-grained (CG) molecular dynamics models is often a laborious process which commonly relies upon approximations to similar models, rather than systematic parametrization. PyCGTOOL automates much of the construction of CG models via calculation of both equilibrium values and force constants of inter...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00096
更新日期:2017-04-24 00:00:00
abstract::The solvation layer surrounding a protein is clearly an intrinsic part of protein structure-dynamics-function, and our understanding of how the hydration dynamics influences protein function is emerging. We have recently reported simulations indicating a correlation between regional hydration dynamics and the structur...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00009
更新日期:2019-05-28 00:00:00
abstract::Rotational Profiler provides an analytical algorithm to compute sets of classical torsional dihedral parameters by fitting an empirical energy profile to a reference one that can be obtained experimentally or by quantum-mechanical methods. The resulting profiles are compatible with the functional forms in the most wid...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c01168
更新日期:2020-12-28 00:00:00
abstract::Many of the conventional similarity methods assume that molecular fragments that do not relate to biological activity carry the same weight as the important ones. One possible approach to this problem is to use the Bayesian inference network (BIN), which models molecules and reference structures as probabilistic infer...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci100232h
更新日期:2011-01-24 00:00:00
abstract::Calcium is involved in important intracellular processes, such as intracellular signaling from cell membrane receptors to the nucleus. Typically, calcium levels are kept at less than 100 nM in the nucleus and cytosol, but some calcium is stored in the endoplasmic reticulum (ER) lumen for rapid release to activate intr...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.6b00475
更新日期:2017-02-27 00:00:00
abstract::In this study we investigate π-stacking interactions of a variety of aromatic heterocycles with benzene using dispersion corrected density functional theory. We calculate extensive potential energy surfaces for parallel-displaced interaction geometries. We find that dispersion contributes significantly to the interact...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci500183u
更新日期:2014-05-27 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::A MMGBSA variant (here referred to as Nwat-MMGBSA), based on the inclusion of a certain number of explicit water molecules (Nwat) during the calculations, has been tested on a set of 20 protein-protein complexes, using the correlation between predicted and experimental binding energy as the evaluation metric. Besides ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.6b00196
更新日期:2016-09-26 00:00:00
abstract::The [H2X2]+ (X = Cl, Br) formula could refer to two possible stable structures, namely, the hydrogen-bonded complex and the three-electron-bonded one. In contrary to the results published by other authors, we claim that for the F-type structures the hydrogen-bonded form is the only possible one and the [HFFH]+ complex...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci600355g
更新日期:2007-05-01 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::Nitric oxide (NO) is an important signaling molecule produced by a family of enzymes called nitric oxide synthases (NOS). Because NO is involved in various pathological conditions, the development of potent and isoform-selective NOS inhibitors is an important challenge. In the present study, the dimer of oxygenase dom...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci100422v
更新日期:2011-06-27 00:00:00
abstract::The membrane permeability of cyclic peptides and peptidomimetics, which are generally larger and more complex than typical drug molecules, is likely strongly influenced by the conformational behavior of these compounds in polar and apolar environments. The size and complexity of peptides often limit their bioavailabil...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.6b00251
更新日期:2016-08-22 00:00:00
abstract::Nonfibrillar neurotoxic amyloid β (Aβ) oligomer structures are typically rich in β-sheets, which could be promoted by metal ions like Zn(2+). Here, using molecular dynamics (MD) simulations, we systematically examined combinations of Aβ40 peptide conformations and Zn(2+) binding modes to probe the effects of secondary...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.5b00063
更新日期:2015-06-22 00:00:00
abstract::Metabolism of xenobiotic and endogenous compounds is frequently complex, not completely elucidated, and therefore often ambiguous. The prediction of sites of metabolism (SoM) can be particularly helpful as a first step toward the identification of metabolites, a process especially relevant to drug discovery. This pape...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400058s
更新日期:2013-06-24 00:00:00
abstract::Development of accurate force field parameters for molecular ions in the context of a polarizable energy function based on the classical Drude oscillator is a crucial step toward an accurate polarizable model for modeling and simulations of biological macromolecules. Toward this goal we have undertaken a hierarchical ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00132
更新日期:2018-05-29 00:00:00
abstract::New hits against HIV-1 wild-type and Y181C drug-resistant reverse transcriptases were predicted taking into account the possibility of some of the known metabolism interactions. In silico hits against a set of antitargets (i.e., proteins or nucleic acids that are off-targets from the desired pharmaceutical target obje...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci200203h
更新日期:2011-10-24 00:00:00
abstract::There are only four derivatives of pseudouridine (Ψ) that are known to occur naturally in RNA as post-transcriptional modifications. We have studied the conformational consequences of pseudouridylation and further modifications using replica exchange molecular dynamics simulations at the nucleoside level, and the simu...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00369
更新日期:2020-10-26 00:00:00
abstract::Class II fructose-1,6-bisphosphate aldolases (FBA-II) are attractive new targets for the discovery of drugs to combat invasive fungal infection, because they are absent in animals and higher plants. Although several FBA-II inhibitors have been reported, none of these inhibitors exhibit antifungal effect so far. In thi...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.6b00763
更新日期:2017-06-26 00:00:00
abstract::We propose predictive performance criteria for nonlinear regression models without cross-validation. The proposed criteria are the determination coefficient and the root-mean-square error for the midpoints between k-nearest-neighbor data points. These criteria can be used to evaluate predictive ability after the regre...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci4003766
更新日期:2013-09-23 00:00:00
abstract::We have studied the binding affinities of a set of 45 small-molecule inhibitors to protein tyrosine phosphatase 1B (PTP1B) through computational approaches. All of these compounds share a common oxalylamino benzoic acid (OBA) moiety. The complex structure of each compound was modeled by using the GOLD program plus the...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci8004429
更新日期:2009-04-01 00:00:00
abstract::We describe a general methodology for designing an empirical scoring function and provide smina, a version of AutoDock Vina specially optimized to support high-throughput scoring and user-specified custom scoring functions. Using our general method, the unique capabilities of smina, a set of default interaction terms ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300604z
更新日期:2013-08-26 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::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