Abstract:
:Physicochemical atomic stereodescriptors (PAS) were implemented that represent the chirality of an atomic chiral center on the basis of empirical physicochemical properties of the ligands. The ligands are ranked according to a specific property, and the chiral center takes an S/R-like descriptor relative to that property. The procedure is performed for a series of properties, yielding a chirality profile. Application of the PAS descriptors to the prediction of enantioselectivity in chemical reactions, from the molecular structures, is illustrated here. The relationship between the molecular structures, represented by the PAS descriptors, and the enantioselectivity was learned by neural networks, decision trees, or random forests. In a first application, a data set was employed with chiral amino alcohols that enantioselectively catalyze the addition of diethylzinc to benzaldehyde. Prediction of the major enantiomer obtained in the reaction, from the molecular structure of the catalyst, was achieved with accuracy up to 90%. The second application investigated the enantiopreference of Pseudomonas cepacia lipase (PCL) toward primary alcohols. The learned models could make correct predictions about the preferred enantiomer, from the molecular structure of the substrate, in up to 93% of the cases. These included substrates with and without O-atoms bonded to the chiral center. The properties automatically selected to build the models can give indications on the relevant factors guiding the observed chemical behavior.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Zhang QY,Aires-de-Sousa Jdoi
10.1021/ci600235wsubject
Has Abstractpub_date
2006-11-01 00:00:00pages
2278-87issue
6eissn
1549-9596issn
1549-960Xjournal_volume
46pub_type
杂志文章abstract::The human DNA-repair O (6)-alkylguanine DNA alkyltransferase (MGMT or hAGT) protein protects DNA from environmental alkylating agents and also plays an important role in tumor resistance to chemotherapy treatment. Available inhibitors, based on pseudosubstrate analogs, have been shown to induce substantial bone marrow...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci700447r
更新日期:2008-04-01 00:00:00
abstract::Mapping the chemical space of small organic molecules is approached from a theoretical graph theory viewpoint, in an effort to begin the systematic exploration of molecular topologies. We present an algorithm for exhaustive generation of scaffold topologies with up to eight rings and an efficient comparison method for...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci7003412
更新日期:2008-07-01 00:00:00
abstract::Representative molecules from 10 classes of prohibited substances were taken from the World Anti-Doping Agency (WADA) list, augmented by molecules from corresponding activity classes found in the MDDR database. Together with some explicitly allowed compounds, these formed a set of 5245 molecules. Five types of fingerp...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci0601160
更新日期:2006-11-01 00:00:00
abstract::Deep learning has demonstrated significant potential in advancing state of the art in many problem domains, especially those benefiting from automated feature extraction. Yet, the methodology has seen limited adoption in the field of ligand-based virtual screening (LBVS) as traditional approaches typically require lar...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00622
更新日期:2020-10-26 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::Among the photophysical parameters that underpin Förster resonance energy transfer (FRET), perhaps the least explored is the spectral overlap term ( J). While by definition J increases linearly with acceptor molar absorption coefficient (ε(A) in M-1 cm-1), is proportional to wavelength (λ4), and depends on the degree ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00753
更新日期:2019-02-25 00:00:00
abstract::Random Forest regression (RF), Partial-Least-Squares (PLS) regression, Support Vector Machines (SVM), and Artificial Neural Networks (ANN) were used to develop QSPR models for the prediction of aqueous solubility, based on experimental data for 988 organic molecules. The Random Forest regression model predicted aqueou...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci060164k
更新日期:2007-01-01 00:00:00
abstract::The current drug virtual screen (VS) methods mainly include two categories. i.e., ligand/target structure-based virtual screen and that, utilizing protein-ligand interaction fingerprint information based on the large number of complex structures. Since the former one focuses on the one-side information while the later...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci200481c
更新日期:2012-03-26 00:00:00
abstract::Protein-ligand (PL) interactions play a key role in many life processes such as molecular recognition, molecular binding, signal transmission, and cell metabolism. Examples of interaction forces include hydrogen bonding, hydrophobic effects, steric clashes, electrostatic contacts, and van der Waals attractions. Curren...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00310
更新日期:2018-01-22 00:00:00
abstract::The configuring of a radial basis function network (RBFN) consists of selecting the network parameters (centers and widths in RBF units and weights between the hidden and output layers) and network architecture. The issues of suboptimum and overfitting, however, often occur in RBFN configuring. This paper presented a ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci600218d
更新日期:2006-11-01 00:00:00
abstract::We present a theoretical study on the performance of ensemble docking methodologies considering multiple protein structures. We perform a theoretical analysis of pose prediction experiments which is completely unbiased, as we make no assumptions about specific scoring functions, search paradigms, protein structures, o...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci2002796
更新日期:2011-11-28 00:00:00
abstract::The consistent handling of molecules is probably the most basic and important requirement in the field of cheminformatics. Reliable results can only be obtained if the underlying calculations are independent of the specific way molecules are represented in the input data. However, ensuring consistency is a complex tas...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400724v
更新日期:2014-03-24 00:00:00
abstract::There is a growing public concern about the lack of reproducibility of experimental data published in peer-reviewed scientific literature. Herein, we review the most recent alerts regarding experimental data quality and discuss initiatives taken thus far to address this problem, especially in the area of chemical geno...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章,评审
doi:10.1021/acs.jcim.6b00129
更新日期:2016-07-25 00:00:00
abstract::How well do different classification methods perform in selecting the ligands of a protein target out of large compound collections not used to train the model? Support vector machines, random forest, artificial neural networks, k-nearest-neighbor classification with genetic-algorithm-optimized feature selection, tren...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci050519k
更新日期:2006-05-01 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::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::In the present work, the Henderson-Hasselbalch (HH) equation has been employed for the development of a tool for the prediction of pH-dependent aqueous solubility of drugs and drug candidates. A new prediction method for the intrinsic solubility was developed, based on artificial neural networks that have been trained...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci600292q
更新日期:2006-11-01 00:00:00
abstract::We report a novel method called ADAN (Applicability Domain ANalysis) for assessing the reliability of drug property predictions obtained by in silico methods. The assessment provided by ADAN is based on the comparison of the query compound with the training set, using six diverse similarity criteria. For every criteri...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci500172z
更新日期:2014-05-27 00:00:00
abstract::Chemical structure extraction from documents remains a hard problem because of both false positive identification of structures during segmentation and errors in the predicted structures. Current approaches rely on handcrafted rules and subroutines that perform reasonably well generally but still routinely encounter s...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00669
更新日期:2019-03-25 00:00:00
abstract::The quantitative structure-activity relationship (QSAR) approach has been used to model a wide range of chemical-induced biological responses. However, it had not been utilized to model chemical-induced genomewide gene expression changes until very recently, owing to the complexity of training and evaluating a very la...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00281
更新日期:2017-09-25 00:00:00
abstract::A data set of 130 diverse compounds containing both central nervous system (CNS) and non-CNS drugs was used to generate a renal clearance model using a classical Volsurf approach. Percentage renal clearance data was used as a biological input. The score plots obtained from principal component analysis and partial leas...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci0503309
更新日期:2006-05-01 00:00:00
abstract::In this account, a rapid retrosynthesis-based scoring method for the assessment of synthetic accessibility of drug-like molecules, called RASA (Retrosynthesis-based Assessment of Synthetic Accessibility) is devised. RASA first constructs a synthesis tree for the target molecule based on retrosynthetic analysis; in thi...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci100216g
更新日期:2011-10-24 00:00:00
abstract::Molecular docking can account for receptor flexibility by combining the docking score over multiple rigid receptor conformations, such as snapshots from a molecular dynamics simulation. Here, we evaluate a number of common snapshot selection strategies using a quality metric from stratified sampling, the efficiency of...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00314
更新日期:2018-09-24 00:00:00
abstract::Protein dynamics play a critical role in ligand binding, and different models have been proposed to explain the relationships between protein motion and molecular recognition. Here, we present a study of ligand-binding processes associated with large conformational changes of a protein to elucidate the critical choice...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00125
更新日期:2017-07-24 00:00:00
abstract::Our recent studies show that the single Tyr residue in the sequence of amyloid-β42 (Aβ42) is reactive toward various ligands, including metals and adenosine trisphospate (see: Coskuner , O. J. Biol. Inorg. Chem. 2016 , 21 , 957 - 973 and Coskuner , O. ; Murray , I. V. J. J. Alzheimer's Dis. 2014 , 41 , 561 - 574 ). Ho...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.6b00761
更新日期:2017-06-26 00:00:00
abstract::Artificial intelligence and multiobjective optimization represent promising solutions to bridge chemical and biological landscapes by addressing the automated de novo design of compounds as a result of a humanlike creative process. In the present study, we conceived a novel pair-based multiobjective approach implement...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00517
更新日期:2020-10-26 00:00:00
abstract::We introduce TICRA (transplant-insert-constrain-relax-assemble), a method for modeling the structure of unknown protein-ligand complexes using the X-ray crystal structures of homologous proteins and ligands with known activity. We present results from modeling the structures of protein kinase-inhibitor complexes using...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci100256u
更新日期:2011-01-24 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::The partitioning of amino acids between water and apolar environments is of vital importance in protein function and drug delivery. Here we present an extensive benchmark for octanol/water (log Poct), chloroform/water (log Pclf), and cyclohexane/water (log Pchx) partition coefficients of neutral amino acid side chain ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00493
更新日期:2018-08-27 00:00:00