Abstract：
:There is a renewed interest in computer-aided synthesis planning, where the vast majority of approaches require the application of retrosynthetic reaction templates. Here we introduce RDChiral, an open-source Python wrapper for RDKit designed to provide consistent handling of stereochemical information in applying retrosynthetic transformations encoded as SMARTS strings. RDChiral is designed to enforce the introduction, destruction, retention, and inversion of chiral tetrahedral centers as well as the cis/trans configuration of double bonds. We also introduce an open-source implementation of a retrosynthetic template extraction algorithm to generate SMARTS patterns from atom-mapped reaction SMILES strings. In this application note, we describe the implementation of these two pieces of code and illustrate their use through many examples.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Coley CW,Green WH,Jensen KFdoi
10.1021/acs.jcim.9b00286subject
Has Abstractpub_date
2019-06-24 00:00:00pages
2529-2537issue
6eissn
1549-9596issn
1549-960Xjournal_volume
59pub_type
杂志文章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：:Template CoMFA, a novel alignment methodology for training or test set structures in 3D-QSAR, is introduced. Its two most significant advantages are its complete automation and its ability to derive a single combined model from multiple structural series affecting a biological target. Its only two inputs are one or mo...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400696v
更新日期：2014-02-24 00:00:00
abstract：:The α2a adrenoceptor is a medically relevant subtype of the G protein-coupled receptor family. Unfortunately, high-throughput techniques aimed at producing novel drug leads for this receptor have been largely unsuccessful because of the complex pharmacology of adrenergic receptors. As such, cutting-edge in silico liga...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c01019
更新日期：2021-01-25 00:00:00
abstract：:Increased reports of oseltamivir (OTV)-resistant strains of the influenza virus, such as the H274Y mutation on its neuraminidase (NA), have created some cause for concern. Many studies have been conducted in the attempt to uncover the mechanism of OTV resistance in H274Y NA. However, most of the reported studies on H2...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00331
更新日期：2016-01-25 00:00:00
abstract：:Sixteen FDA-approved drugs were investigated to elucidate their mechanisms of action (MOAs) and clinical functions by pathway analysis based on retrieved drug targets interacting with or affected by the investigated drugs. Protein and gene targets and associated pathways were obtained by data-mining of public database...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci4005354
更新日期：2014-02-24 00:00:00
abstract：:Given the essential role played by protein kinases in regulating cellular pathways, their dysregulation can result in the onset and/or progression of various human diseases. Structural analysis of diverse protein kinases suggests that these proteins exhibit a remarkable plasticity that allows them to adopt distinct co...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00439
更新日期：2017-10-23 00:00:00
abstract：:In this study, two probabilistic machine-learning algorithms were compared for in silico target prediction of bioactive molecules, namely the well-established Laplacian-modified Naïve Bayes classifier (NB) and the more recently introduced (to Cheminformatics) Parzen-Rosenblatt Window. Both classifiers were trained in ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300435j
更新日期：2013-08-26 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：:We report the synthesis and a study of the structure-activity relationships of a new series of diarylhydrazides as potential selective non-ligand binding pocket androgen receptor antagonists. Their biological activity as antiandrogens in the context of the development of treatments for castration resistant prostate ca...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400189m
更新日期：2013-08-26 00:00:00
abstract：:Molecular fingerprints are widely used for similarity-based virtual screening in drug discovery projects. In this paper we discuss the performance and the complementarity of nine two-dimensional fingerprints (Daylight, Unity, AlFi, Hologram, CATS, TRUST, Molprint 2D, ChemGPS, and ALOGP) in retrieving active molecules ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci0504723
更新日期：2006-05-01 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：: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：:In this study, in order to elucidate the action mechanism of traditional Chinese medicines (TCMs) that exhibit clinical efficacy for type II diabetes mellitus (T2DM), an integrated protocol that combines molecular docking and pharmacophore mapping was employed to find the potential inhibitors from TCM for the T2DM-rel...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400146u
更新日期：2013-07-22 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：: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：: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：:Deep learning methods applied to problems in chemoinformatics often require the use of recursive neural networks to handle data with graphical structure and variable size. We present a useful classification of recursive neural network approaches into two classes, the inner and outer approach. The inner approach uses r...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00384
更新日期：2018-02-26 00:00:00
abstract：:Classical nonpolarizable models, normally based on a combination of Lennard-Jones sites and point charges, are extensively used to model thermodynamic properties of fluids, including solvation. An important shortcoming of these models is that they do not explicitly account for polarization effects, i.e., a description...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b01005
更新日期：2020-03-23 00:00:00
abstract：:The conformational properties of AT1 antagonist valsartan have been analyzed both in solution and at the binding site of the receptor. Low energy conformations of valsartan in solution were explored by NMR spectroscopy and molecular modeling studies. The NMR results showed the existence of two distinct and almost isoe...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800427s
更新日期：2009-03-01 00:00:00
abstract：:Iterative screening has emerged as a promising approach to increase the efficiency of high-throughput screening (HTS) campaigns in drug discovery. By learning from a subset of the compound library, inferences on what compounds to screen next can be made by predictive models. One of the challenges of iterative screenin...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00724
更新日期：2019-03-25 00:00:00
abstract：:Target-oriented substructure-based virtual screening (sSBVS) of molecules is a promising approach in drug discovery. Yet, there are doubts whether sSBVS is suitable also for extrapolation, that is, for detecting molecules that are very different from those used for training. Herein, we evaluate the predictive power of...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci200472s
更新日期：2012-03-26 00:00:00
abstract：:The recent article "Evaluation of pK(a) Estimation Methods on 211 Druglike Compounds" ( Manchester, J.; et al. J. Chem Inf. Model. 2010, 50, 565-571 ) reports poor results for the program Epik. Here, we highlight likely sources for the poor performance and describe work done to improve the performance. Running Epik in...
journal_title：Journal of chemical information and modeling
pub_type： 评论,杂志文章
doi：10.1021/ci100332m
更新日期：2011-01-24 00:00:00
abstract：:Functional diversity of the three-finger-protein domain (TFPD) had been acquired via hypervariability of some sequence positions and extensive insertion/deletion of short AA-segments that caused multidimensional drift of several sequence attributes such as the overall (HI) and local hydrophobicity levels, the isoelect...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00322
更新日期：2015-09-28 00:00:00
abstract：:Inhibitors of histone deacetylases (HDACIs) have emerged as a new class of drugs for the treatment of human cancers and other diseases because of their effects on cell growth, differentiation, and apoptosis. In this study we have developed several quantitative structure-activity relationship (QSAR) models for 59 chemi...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800366f
更新日期：2009-02-01 00:00:00
abstract：:Traditional herbal medicine has been an inseparable part of the traditional medical science in many countries throughout history. Nowadays, the popularity of using herbal medicines in daily life, as well as clinical practices, has gradually expanded to numerous Western countries with positive impacts and acceptance. T...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00826
更新日期：2020-03-23 00:00:00
abstract：:Membrane fusion, a key step in the early stages of virus propagation, allows the release of the viral genome in the host cell cytoplasm. The process is initiated by fusion peptides that are small, hydrophobic components of viral membrane-embedded glycoproteins and are typically conserved within virus families. Here, w...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c01231
更新日期：2021-01-25 00:00:00
abstract：:The high-throughput docking protocol called ALTA-VS (anchor-based library tailoring approach for virtual screening) was developed in 2005 for the efficient in silico screening of large libraries of compounds by preselection of only those molecules that have optimal fragments (anchors) for the protein target. Here we p...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00336
更新日期：2017-10-23 00:00:00
abstract：:The efficiency of automated compound screening is heavily influenced by the design and the quality of the screening libraries used. We recently reported on the assembly of one diverse and one target-focused lead-like screening library. Using data from 15 enzyme-based screenings conducted using these libraries, their p...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300382f
更新日期：2013-03-25 00:00:00
abstract：:Targeted covalent inhibitors (TCIs) have been successfully developed as high-affinity and selective inhibitors of enzymes of the protein kinase family. These drugs typically act by undergoing an electrophilic addition with an active-site cysteine residue, so design of a TCI begins with the identification of a "druggab...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00454
更新日期：2018-09-24 00:00:00
abstract：:The applicability and scope of 3D QSAR methods (CoMFA, CoMSIA) to screen databases are examined. A protocol requiring minimal user intervention has been established to align training and test set molecules using FlexS. As model system isozymes of human carbonic anhydrase (hCA) are used, all results are exemplified stu...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci7002945
更新日期：2008-02-01 00:00:00
