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 p38 and Lck as examples. These examples show that the TICRA method may be used prospectively to create and refine models for protein kinase-inhibitor complexes with an overall backbone rmsd of less than 0.75 Å for the kinase domain, when compared to published X-ray crystal structures. Further refinement of the models of the kinase domains of p38 and Lck in complex with their cognate ligands from the published crystal structures was able to improve the rmsd's of the model complexes to below 0.5 Å. Our results show that TICRA is a useful approach to the problem of structure-based drug design in cases where little structural information is available for the target proteins and the binding mode of active compounds is unknown.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Meshkat S,Klon AE,Zou J,Wiseman JS,Konteatis Zdoi
10.1021/ci100256usubject
Has Abstractpub_date
2011-01-24 00:00:00pages
52-60issue
1eissn
1549-9596issn
1549-960Xjournal_volume
51pub_type
杂志文章abstract：:The modeling of nonlinear descriptor-target relationships is a topic of considerable interest in drug discovery. We, herein, continue reporting the use of the self-organizing map-a nonlinear, topology-preserving pattern recognition technique that exhibits considerable promise in modeling and decoding these relationshi...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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abstract：:The semiempirical quantum mechanical (SQM) methods used in drug design are commonly parametrized and tested on data sets of systems that may not be representative models for drug-biomolecule interactions in terms of both size and chemical composition. This is addressed here with a new benchmark data set, PLF547, deriv...
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journal_title：Journal of chemical information and modeling
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更新日期：2018-06-25 00:00:00
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pub_type： 杂志文章
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abstract：:While critically reviewing the current status of what is known about C28H14 and C30H14 benzenoid isomers, which are ubiquitous pyrolytic constituents, some new insights will be presented. Representative isomers belonging to these benzenoid hydrocarbons are at the crossroads to homologous series that extend to infinite...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050298i
更新日期：2006-03-01 00:00:00
abstract：:Support vector regression (SVR) is a premier approach for the prediction of compound potency. Given the conceptual link between support vector machine (SVM) and SVR modeling, SVR is capable of accounting for continuous and discontinuous structure-activity relationships (SARs) in potency prediction, which further exten...
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pub_type： 杂志文章
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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abstract：:We present our newly developed and highly efficient lossless compression algorithm for trajectories of atom positions and volumetric data. The algorithm is designed as a two-step approach. In the first step, efficient polynomial extrapolation schemes reduce the information entropy of the data by exploiting both spatia...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00501
更新日期：2018-10-22 00:00:00
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更新日期：2007-09-01 00:00:00
abstract：:QSPR studies, using scores of SciTegic's extended connectivity fingerprint as raw descriptors, were extended to the prediction of melting points and aqueous solubility of organic compounds. Robust partial least-squares models were developed that perform as well as the best published QSPR models for structurally divers...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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更新日期：2008-05-01 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：:Pharmacophore hypotheses were developed for six structurally diverse series of cholecystokinin-B/gastrin receptor (CCK-BR) antagonists. A training set consisting of 33 compounds was carefully selected. The activity spread of the training set molecules was from 0.1 to 2100 nM. The most predictive pharmacophore model (h...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050257m
更新日期：2005-11-01 00:00:00
abstract：:In this study, we used the Martini Coarse-Grained model with no applied restraints to predict the binding mode of some peptides to G-Protein Coupled Receptors (GPCRs). Both the Neurotensin-1 and the chemokine CXCR4 receptors were used as test cases. Their ligands, NTS8-13 and CVX15 peptides, respectively, were initial...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00503
更新日期：2017-03-27 00:00:00
abstract：:3-Pyridyl ethers are excellent nAChRs ligands, which show high subtype selectivity and binding affinity to alpha4beta2 nAChR. Although the quantitative structure-activity relationship (QSAR) of nAChRs ligands has been widely investigated using various classes of compounds, the open ring analogues of 3-pyridyl ethers h...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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更新日期：2005-03-01 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
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00951
更新日期：2020-12-28 00:00:00
abstract：:The human cytochrome P450 1A2 is an important drug metabolizing and procarcinogen activating enzyme. An experimental study found that a peripheral mutation, F186L, at ∼26 Å away from the enzyme's active site, caused a significant reduction in the enzymatic activity of 1A2 deethylation reactions. In this paper, we expl...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci200112b
更新日期：2011-06-27 00:00:00
abstract：:Encapsulation of peptide and protein-based drugs in polymeric nanoparticles is one of the fundamental fields in controlled-release drug delivery systems. The molecular mechanisms of absorption of peptides to the polymeric nanoparticles are still unknown, and there is no precise molecular data on the encapsulation proc...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00641
更新日期：2019-01-28 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00926
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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
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更新日期：2017-09-25 00:00:00
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更新日期：2006-05-01 00:00:00
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journal_title：Journal of chemical information and modeling
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更新日期：2015-12-28 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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更新日期：2010-09-27 00:00:00
abstract：:Aβ25-35 is a short, cytotoxic, and naturally occurring fragment of the Alzheimer's Aβ peptide. To map the molecular mechanism of Aβ25-35 binding to the zwitterionic dimyristoylphosphatidylcholine (DMPC) bilayer, we have performed replica exchange with solute tempering molecular dynamics simulations using all-atom expl...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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更新日期：2018-05-29 00:00:00
abstract：:In the preceding paper (Duca, J. S.; Madison, V. S.; Voigt, J. H. J. Chem. Inf. Model. 2008, 48, 659-668), the accuracy of docking and affinity predictions of the Gold and Glide programs were investigated using single protein conformations spanning 150 CDK2/inhibitor crystallographic complexes. High docking accuracy w...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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更新日期：2008-03-01 00:00:00
abstract：:Herein we present the VMD Store, an open-source VMD plugin that simplifies the way that users browse, discover, install, update, and uninstall extensions for the Visual Molecular Dynamics (VMD) software. The VMD Store obtains data about all the indexed VMD extensions hosted on GitHub and presents a one-click mechanism...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00739
更新日期：2019-11-25 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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更新日期：2018-05-29 00:00:00
abstract：:A major concern of chemogenomics is to associate drug activity with biological variables. Several reports have clustered cell line drug activity profiles as well as drug activity-gene expression correlation profiles and noted that the resulting groupings differ but still reflect mechanism of action. The present paper ...
journal_title：Journal of chemical information and modeling
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更新日期：2007-01-01 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
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更新日期：2012-03-26 00:00:00
abstract：:Virtual screening is a powerful methodology to search for new small molecule inhibitors against a desired molecular target. Usually, it involves evaluating thousands of compounds (derived from large databases) in order to select a set of potential binders that will be tested in the wet-lab. The number of tested compou...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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更新日期：2017-08-28 00:00:00
