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::We present an algorithm, ReFlex3D, for the refinement of flexible molecular alignments based on their three-dimensional shape and electrostatic properties. The algorithm is designed to be used with fast conformer generators to refine an initial overlay between two molecules and thus to obtain improved overlaps as judg...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00618
更新日期:2018-04-23 00:00:00
abstract::Derivation of structure-kinetics relationships can help rational design and development of new small-molecule drug candidates with desired residence times. Efforts are now being directed toward the development of efficient computational methods. Currently, there is a lack of solid, high-throughput binding kinetics pre...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00450
更新日期:2020-12-28 00:00:00
abstract::Cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphoshatase (cy-FBP/SBPase) is a potential enzymatic target for screening of novel inhibitors that can combat harmful algal blooms. In the present study, we targeted the substrate binding pocket of cy-FBP/SBPase. A series of novel hit compounds from the SPECs database w...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci4007529
更新日期:2014-03-24 00:00:00
abstract::Identifying sequence modifications that distinguish psychrophilic from mesophilic proteins is important for designing enzymes with different thermodynamic stabilities and to understand the underlying mechanisms. The PoPMuSiC algorithm is used to introduce, in silico, all the single-site mutations in four mesophilic an...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci050473v
更新日期:2006-05-01 00:00:00
abstract::Reaction classification has important applications, and many approaches to classification have been applied. Our own algorithm tests all maximum common substructures (MCS) between all reactant and product molecules in order to find an atom mapping containing the minimum chemical distance (MCD). Recent publications hav...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400442f
更新日期:2013-11-25 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::CYP19A1, also known as aromatase or estrogen synthetase, is the rate-limiting enzyme in the biosynthesis of estrogens from their corresponding androgens. Several clinically used breast cancer therapies target aromatase. In this work, explicitly solvated all-atom molecular dynamics simulations of aromatase with a model...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400225w
更新日期:2013-08-26 00:00:00
abstract::Whereas 400 million distinct compounds are now purchasable within the span of a few weeks, the biological activities of most are unknown. To facilitate access to new chemistry for biology, we have combined the Similarity Ensemble Approach (SEA) with the maximum Tanimoto similarity to the nearest bioactive to predict a...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00316
更新日期:2018-01-22 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::Drug-induced torsade de pointes (TdP) is a life-threatening ventricular arrhythmia responsible for the withdrawal of many drugs from the market. Although currently used TdP risk-assessment methods are effective, they are expensive and prone to produce false positives. In recent years, in silico cardiac simulations hav...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00201
更新日期:2020-10-26 00:00:00
abstract::The similarity/diversity measures play a fundamental role in library searching, virtual screening, and quantitative structure-activity relationship/quantitative structure-property relationship modeling as well as in genomics and proteomics. In this paper, a new similarity/diversity measure is proposed as a new approac...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci060099e
更新日期:2006-09-01 00:00:00
abstract::Reversible and irreversible covalent ligands are advanced cysteine protease inhibitors in the drug development pipeline. K777 is an irreversible inhibitor of cruzain, a necessary enzyme for the survival of the Trypanosoma cruzi (T. cruzi) parasite, the causative agent of Chagas disease. Despite their importance, irrev...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b01138
更新日期:2020-03-23 00:00:00
abstract::Increasing protein kinase C (PKC) activity is of potential therapeutic value. Its activation involves an interaction between the C1 domain and diacylglycerol (DAG) at intracellular membrane surfaces; DAG mimetics hold promise as new drugs. We previously developed the isophthalate derivative HMI-1a3, an effective but h...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00624
更新日期:2020-11-23 00:00:00
abstract::Retrieving molecules with specific structural features is a fundamental requirement of today's molecular database technologies. Estimates claim the chemical space relevant for drug discovery to be around 10⁶⁰ molecules. This figure is many orders of magnitude larger than the amount of molecules conventional databases ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400107k
更新日期:2013-07-22 00:00:00
abstract::Sterol 14α-demethylase (CYP51) is the main drug target for the treatment of fungal infections. The discovery of new efficient fungal CYP51 inhibitors requires an understanding of the structural requirements for selectivity for the fungal over the human ortholog. In this study, a binding mode of the pyridylethanol(phen...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci500556k
更新日期:2014-12-22 00:00:00
abstract::The concept of chemoisosterism of protein environments is introduced as the complementary property to bioisosterism of chemical fragments. In the same way that two chemical fragments are considered bioisosteric if they can bind to the same protein environment, two protein environments will be considered chemoisosteric...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci3002974
更新日期:2013-02-25 00:00:00
abstract::Pharmacophore search is a key component of many drug discovery efforts. Pharmer is a new computational approach to pharmacophore search that scales with the breadth and complexity of the query, not the size of the compound library being screened. Two novel methods for organizing pharmacophore data, the Pharmer KDB-tre...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci200097m
更新日期:2011-06-27 00:00:00
abstract::Fragment-based methods have emerged in the last two decades as alternatives to traditional high throughput screenings for the identification of chemical starting points in drug discovery. One arguable yet popular assumption about fragment-based design is that the fragment binding mode remains conserved upon chemical e...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300355p
更新日期:2012-12-21 00:00:00
abstract::Protein-ligand binding is essential to almost all life processes. The understanding of protein-ligand interactions is fundamentally important to rational drug and protein design. Based on large scale data sets, we show that protein rigidity strengthening or flexibility reduction is a mechanism in protein-ligand bindin...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00226
更新日期:2017-07-24 00:00:00
abstract::Reactive oxygen species such as superoxide are potentially harmful byproducts of the aerobic metabolism in the inner mitochondrial membrane, and complexes I, II, III of the electron transport chain have been identified as primary sources. The mitochondrial fatty acid b-oxidation pathway may also play a yet uncharacter...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00702
更新日期:2019-11-25 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::This work is aimed at describing the workflow for a methodology that combines chemoinformatics and pharmacoepidemiology methods and at reporting the first predictive model developed with this methodology. The new model is able to predict complex networks of AIDS prevalence in the US counties, taking into consideration...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400716y
更新日期:2014-03-24 00:00:00
abstract::Partial covalent interactions (PCIs) in proteins, which include hydrogen bonds, salt bridges, cation-π, and π-π interactions, contribute to thermodynamic stability and facilitate interactions with other biomolecules. Several score functions have been developed within the Rosetta protein modeling framework that identif...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00398
更新日期:2018-05-29 00:00:00
abstract::A model for prediction of percent intestinal absorption (%Abs) of neutral molecules was developed based upon surface charges of the molecule calculated by density functional theory (DFT). The surface charges are decomposed into sigma moments which are correlated to a partition coefficient representing transfer of the ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci049653f
更新日期:2005-09-01 00:00:00
abstract::Mass spectrometric data are copious and generate a processing burden that is best dealt with programmatically. PythoMS is a collection of tools based on the Python programming language that assist researchers in creating figures and video output that is informative, clear, and visually compelling. The PythoMS framewor...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00055
更新日期:2019-04-22 00:00:00
abstract::The protonation states for nucleic acid bases are difficult to assess experimentally. In the context of DNA triplex, the protonation state of cytidine in the third strand is particularly important, because it needs to be protonated in order to form Hoogsteen hydrogen bonds. A sugar modification, locked nucleic acid (L...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00741
更新日期:2018-04-23 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 momentum gained by research on biologics has not been met yet with equal thrust on the informatics side. There is a noticeable lack of software for data management that empowers the bench scientists working on the development of biologic therapeutics. SARvision|Biologics is a tool to analyze data associated with b...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400333x
更新日期:2013-10-28 00:00:00
abstract::A novel approach was developed to rationally interface structure- and ligand-based drug design through the rescoring of docking poses and automated generation of molecular alignments for 3D quantitative structure-activity relationship investigations. The procedure was driven by a genetic algorithm optimizing the value...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci800015s
更新日期:2008-06-01 00:00:00
abstract::We investigate unexpectedly short non-covalent distances (<85% of the sum of van der Waals radii) in X-ray crystal structures of proteins. We curate over 11 000 high-quality protein crystal structures and an ultra-high-resolution (1.2 Å or better) subset containing >900 structures. Although our non-covalent distance c...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00144
更新日期:2019-05-28 00:00:00