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 of a novel fitness function, accounting simultaneously for best regressions among binding-energy docking scores and affinities and for minimal geometric deviations from properly established crystal-based binding geometry. The GRID/CPCA method, as implemented in GOLPE, was used to feature molecular determinants of ligand binding affinity for each molecular alignment. In addition, unlike standard procedures, a novel multipoint equation was adopted to predict the binding affinity of ligands in the prediction set. Selectivity was investigated through square plots reporting experimental versus recalculated binding affinities on the targets under examination. The application of our approach to the modeling of affinity data of a large series of 3-amidinophenylalanine inhibitors of thrombin, trypsin, and factor Xa generated easily interpretable and independent models with robust statistics. As a further validation study, our approach was successfully applied to a series of 3,4,7-substituted coumarins, acting as selective MAO-B inhibitors.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Nicolotti O,Miscioscia TF,Carotti A,Leonetti F,Carotti Adoi
10.1021/ci800015ssubject
Has Abstractpub_date
2008-06-01 00:00:00pages
1211-26issue
6eissn
1549-9596issn
1549-960Xjournal_volume
48pub_type
杂志文章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
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journal_title：Journal of chemical information and modeling
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journal_title：Journal of chemical information and modeling
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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更新日期：2015-01-26 00:00:00
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journal_title：Journal of chemical information and modeling
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journal_title：Journal of chemical information and modeling
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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journal_title：Journal of chemical information and modeling
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00135
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700016d
更新日期：2007-07-01 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci5002372
更新日期：2014-06-23 00:00:00
abstract：:In structure-based drug design, scoring functions are often employed to evaluate protein-ligand interactions. A variety of scoring functions have been developed so far, and thus, some objective benchmarks are desired for assessing their strength and weakness. The comparative assessment of scoring functions (CASF) benc...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00545
更新日期：2019-02-25 00:00:00
abstract：:Several hypotheses to elucidate the linkage isomer preference of the thiocyanate (SCN(-)) ion have been offered. For complexes with small coordination numbers (i.e., 1 and 2) and groups 11 (Cu-triad) and 12 (Zn-triad) metals, different levels of theory and a variety of basis sets have been employed to study linkage is...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050050t
更新日期：2005-07-01 00:00:00
abstract：:To promote more productive combinatorial endeavors, the Diversity Space methodology introduced here enables similarity comparisons at the library level. Particularly at an early screening stage, when little or no information is available regarding the pharmacophoric entities necessary for binding, it is more efficient...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci060066z
更新日期：2006-07-01 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 信件
doi：10.1021/acs.jcim.8b00193
更新日期：2018-06-25 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400147s
更新日期：2013-05-24 00:00:00
abstract：:We have performed a systematic study of the entropy term in the MM/GBSA (molecular mechanics combined with generalized Born and surface-area solvation) approach to calculate ligand-binding affinities. The entropies are calculated by a normal-mode analysis of harmonic frequencies from minimized snapshots of molecular d...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci3001919
更新日期：2012-08-27 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
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更新日期：2011-01-24 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：:3-Phosphoinositide-dependent protein kinase-1 (PDK1) is a promising target for developing novel anticancer drugs. In order to understand the structure-activity correlation of indolinone-based PDK1 inhibitors, we have carried out a combined molecular docking and three-dimensional quantitative structure-activity relatio...
journal_title：Journal of chemical information and modeling
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00704
更新日期：2019-02-25 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400400m
更新日期：2013-11-25 00:00:00
abstract：:In this work, the perception of similarity of reactions catalyzed by hydrolases and oxidoreductases on the basis of the overall breaking and making of bonds of reactions is investigated. Six physicochemical properties for the reacting bond in the substrate of each enzymatic reaction were calculated to describe the cha...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci9004833
更新日期：2010-06-28 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：:Throughout the drug discovery process, discovery teams are compelled to use statistics for making decisions using data from a variety of inputs. For instance, teams are asked to prioritize compounds for subsequent stages of the drug discovery process, given results from multiple screens. To assist in the prioritizatio...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci600556v
更新日期：2007-05-01 00:00:00
abstract：:The ongoing search for fast Li-ion conducting solid electrolytes has driven the deployment surge on density functional theory (DFT) computation and materials informatics for exploring novel chemistries before actual experimental testing. Existing structure prototypes can now be readily evaluated beforehand not only to...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500752n
更新日期：2015-06-22 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：:A phenotypic screen (PS) is used to identify compounds causing a desired phenotype in a complex biological system where mechanisms and targets are largely unknown. Deconvoluting the mechanism of action of actives and identification of relevant targets and pathways remains a formidable challenge. Current methods fail t...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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更新日期：2014-02-24 00:00:00
abstract：:Solute-solvent interactions are critical for biomolecular stability and recognition. Explicit solvent molecular dynamics (MD) simulations are routinely used to probe such interactions. However, detailed analyses and interpretation of the hydration patterns seen in MD simulations can be both complex and time-consuming....
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00453
更新日期：2019-07-22 00:00:00
