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 objective) are used to predict a simple, visual measure of possible interactions for the ligands, which helps to introduce early safety considerations into the design of compounds before lead optimization. This combined approach consists of consensus docking and scoring: cross-docking to a group of wild-type and drug-resistant mutant proteins, ligand efficiency (also called binding efficiency) indices as new ranking measures, pre- and postdocking filters, a set of antitargets and estimation, and minimization of atomic clashes. Diverse, small-molecule compounds with new chemistry (such as a triazine core with aromatic side chains) as well as known drugs for different applications (oxazepam, chlorthalidone) were highly ranked to the targets having binding interactions and functional group spatial arrangements similar to those of known inhibitors, while being moderate to low binders to the antitargets. The results are discussed on the basis of their relevance to medicinal and computational chemistry. Optimization of ligands to targets and off-targets or antitargets is foreseen to be critical for compounds directed at several simultaneous sites.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
García-Sosa AT,Sild S,Takkis K,Maran Udoi
10.1021/ci200203hsubject
Has Abstractpub_date
2011-10-24 00:00:00pages
2595-611issue
10eissn
1549-9596issn
1549-960Xjournal_volume
51pub_type
杂志文章abstract：:Predictive metabolism methods can be used in drug discovery projects to enhance the understanding of structure-metabolism relationships. The present study uses data mining methods to exploit biotransformation data that have been recorded in the MDL Metabolite database. Reacting center fingerprints were derived from a ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci600376q
更新日期：2007-03-01 00:00:00
abstract：:Engineered nanomaterials (ENMs) are increasingly infiltrating our lives as a result of their applications across multiple fields. However, ENM formulations may result in the modulation of pathways and mechanisms of toxic action that endanger human health and the environment. Alternative testing methods such as in sili...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00223
更新日期：2017-09-25 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：:Dynamical properties of proteins play an essential role in their function exertion. The elastic network model (ENM) is an effective and efficient tool in characterizing the intrinsic dynamical properties encoded in biomacromolecule structures. The Gaussian network model (GNM) and anisotropic network model (ANM) are th...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c01178
更新日期：2021-01-26 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：:We demonstrate that using an all-atom molecular mechanics force field combined with an implicit solvent model for scoring protein-ligand complexes is a promising approach for improving inhibitor enrichment in the virtual screening of large compound databases. The rescoring method is evaluated by the extent to which kn...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci0502855
更新日期：2006-01-01 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：: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：:The programs Phase and Catalyst HypoGen are compared for their performance in determining three-dimensional quantitative structure-activity relationships. Eight sets of compounds with measured activity were collected from the public literature and partitioned into suitable training and test sets by an automated proced...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci7000082
更新日期：2007-05-01 00:00:00
abstract：:Various cages are constructed by using three types of caps: f-cap (derived from spherical fullerenes by deleting zones of various size), kf-cap (obtainable by cutting off the polar ring, of size k), and t-cap ("tubercule"-cap). Building ways are presented, some of them being possible isomerization routes in the real c...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci049738g
更新日期：2005-03-01 00:00:00
abstract：:In this work, we present a systematical investigation of the influence of ligand protonation states, stereoisomers, and tautomers on results obtained with the two protein-ligand docking programs GOLD and PLANTS. These different states were generated with a fully automated tool, called SPORES (Structure PrOtonation and...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800420z
更新日期：2009-06-01 00:00:00
abstract：:Virtual screening is routinely used to discover new ligands and in particular new ligand chemotypes for G protein-coupled receptors (GPCRs). To prepare for a virtual screen, we often tailor a docking protocol that will enable us to select the best candidates for further screening. To aid this, we created GPCR-Bench, a...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00660
更新日期：2016-04-25 00:00:00
abstract：:An in silico screening procedure was performed to select new inhibitors of glycogen synthase kinase 3β (GSK-3β), a serine/threonine protein kinase that in the last two decades has emerged as a key target in drug discovery, having been implicated in multiple cellular processes and linked with the pathogenesis of severa...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00486
更新日期：2015-12-28 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：:The Torsion Library contains hundreds of rules for small molecule conformations which have been derived from the Cambridge Structural Database (CSD) and are curated by molecular design experts. The torsion rules are encoded as SMARTS patterns and categorize rotatable bonds via a traffic light coloring scheme. We have ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00522
更新日期：2016-01-25 00:00:00
abstract：:The binding affinity and relative maximal efficacy of human A3 adenosine receptor (AR) agonists were each subjected to ligand-based three-dimensional quantitative structure-activity relationship analysis. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) used a...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci600501z
更新日期：2007-05-01 00:00:00
abstract：:Screening large libraries of chemicals has been an efficient strategy to discover bioactive compounds; however a portion of the potential for success is limited to the available libraries. Synergizing combinatorial and computational chemistries has emerged as a time-efficient strategy to explore the chemical space mor...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00648
更新日期：2017-03-27 00:00:00
abstract：:Reversible covalent inhibitors have drawn increasing attention in drug design, as they are likely more potent than noncovalent inhibitors and less toxic than covalent inhibitors. Despite those advantages, the computational prediction of reversible covalent binding presents a formidable challenge because the binding pr...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00959
更新日期：2019-05-28 00:00:00
abstract：:On the order of hundreds of absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) models have been described in the literature in the past decade which are more often than not inaccessible to anyone but their authors. Public accessibility is also an issue with computational models for bioactivity, a...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00143
更新日期：2015-06-22 00:00:00
abstract：:Human cannabinoid type 1 (CB1) G-protein coupled receptor is a potential therapeutic target for obesity. The previously predicted and experimentally validated ensemble of ligand-free conformations of CB1 [Scott, C. E. et al. Protein Sci. 2013 , 22 , 101 - 113 ; Ahn, K. H. et al. Proteins 2013 , 81 , 1304 - 1317] are u...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00581
更新日期：2016-01-25 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：:The present study focuses on the determination of the biologically significant N-acetylneuraminic acid (NANA) drug binding interaction mechanism between bovine serum albumin (BSA) and human α-1 acid glycoprotein (HAG) using various optical spectroscopy and computational methods. The steady state fluorescence spectrosc...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00558
更新日期：2019-01-28 00:00:00
abstract：:The possibility of improving the predictive ability of comparative molecular field analysis (CoMFA) by settings optimization has been evaluated to show that CoMFA predictive ability can be improved. Ten different CoMFA settings are evaluated, producing a total of 6120 models. This method has been applied to nine diffe...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci049612j
更新日期：2006-01-01 00:00:00
abstract：:Protein farnesyltransferase (FTase) is an important anticancer drug target. In an effort to develop isoprenoid diphosphate-based FTase inhibitors, striking variations have been observed in the ability of conservatively modified analogues to bind to the enzyme. For example, 2Z-GGPP is an alternative substrate with high...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci0496550
更新日期：2005-07-01 00:00:00
abstract：:Reduction of the affinity of the fragment crystallizable (Fc) region with immune receptors by substitution of one or a few amino acids, known as Fc-silencing, is an established approach to reduce the immune effector functions of monoclonal antibody therapeutics. This approach to Fc-silencing, however, is problematic a...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b01198
更新日期：2020-11-23 00:00:00
abstract：:The study of chromatographic retention of natural products can be used to increase their identification speed in complex biological matrices. In this work, six variables were used to study the retention behavior in reversed phase liquid chromatography of 39 sesquiterpene lactones (SL) from an in-house database using c...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500581q
更新日期：2015-01-26 00:00:00
abstract：:Naturally occurring anticancer compounds represent about half of the chemotherapeutic drugs which have been put in the market against cancer until date. Computer-based or in silico virtual screening methods are often used in lead/hit discovery protocols. In this study, the "drug-likeness" of ~400 compounds from Africa...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci5003697
更新日期：2014-09-22 00:00:00
abstract：:Designing organic saccharide sensors for use in aqueous solution is a nontrivial endeavor. Incorporation of hydrogen bonding groups on a sensor's receptor unit to target saccharides is an obvious strategy but not one that is likely to ensure analyte-receptor interactions over analyte-solvent or receptor-solvent intera...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00987
更新日期：2019-05-28 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：: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
