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 known binders for nine diverse, therapeutically relevant enzymes are enriched against a background of approximately 100,000 drug-like decoys. The improvement in enrichment is most robust and dramatic within the top 1% of the ranked database, that is, the first thousand compounds; below the first few percent of the ranked database, there is little overall improvement. The improved early enrichment is likely due to the more realistic treatment of ligand and receptor desolvation in the rescoring procedure. We also present anecdotal but encouraging results assessing the ability of the rescoring method to predict specificity of inhibitors for structurally related proteins.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Huang N,Kalyanaraman C,Irwin JJ,Jacobson MPdoi
10.1021/ci0502855keywords:
subject
Has Abstractpub_date
2006-01-01 00:00:00pages
243-53issue
1eissn
1549-9596issn
1549-960Xjournal_volume
46pub_type
杂志文章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：:In this work, we present molecular modeling studies carried out using six DNA sequences and six azinomycin analogues, including the naturally occurring compound azinomycin B, selected on the basis of known cell cytotoxicity and structural analogies (epoxide and aziridine alkylating moieties). Among several computation...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci0496595
更新日期：2005-05-01 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：:Most of the common molecular descriptors have numerous different implementations. This can influence the results of compound prioritization based on the multiparameter assessment (MPA) approach that allows a medicinal chemist to simultaneously analyze and achieve the desired balance of the diverse and often conflictin...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00734
更新日期：2018-05-29 00:00:00
abstract：:Aminoglycosides are antibiotics targeting the 16S RNA A site of the bacterial ribosome. There have been many efforts directed toward design of their synthetic derivatives, however with only few successes. As RNA binders, aminoglycosides are also a difficult target for computational drug design, since most of the exist...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800361a
更新日期：2009-02-01 00:00:00
abstract：:A new radial space-filling method for visualizing cluster hierarchies is presented. The method, referred to as a radial clustergram, arranges the clusters into a series of layers, each representing a different level of the tree. It uses adjacency of nodes instead of links to represent parent-child relationships and al...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci600427x
更新日期：2007-01-01 00:00:00
abstract：:The recognition of peptide/MHC by T-cell receptors is one of the most important interactions in the adaptive immune system. A large number of computational studies have investigated the structural dynamics of this interaction. However, to date only limited attention has been paid to differences between the dynamics of...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00511
更新日期：2016-01-25 00:00:00
abstract：:Saturated acyclic alkanes show steric strain if they are highly branched and, in extreme cases, fall apart rapidly at room temperature. Consequently, attempts to count the number of isomeric forms for a given molecular formula that neglect this physical consideration will inevitably overestimate the size of the availa...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700246b
更新日期：2007-11-01 00:00:00
abstract：:The effects of paclitaxel (PTX) loading fraction and spatial PTX arrangement on poly(γ-glutamyl-glutamate) paclitaxel (PGG-PTX) aggregation were explored using coarse-grained molecular dynamics. Results show that the PTX loading fraction does not significantly impact aggregation, and the spatial PTX arrangement only a...
journal_title：Journal of chemical information and modeling
pub_type： 信件
doi：10.1021/ci200214m
更新日期：2011-12-27 00:00:00
abstract：:Acetohydroxyacid synthase (AHAS) is a thiamin diphosphate-dependent enzyme involved in the biosynthesis of valine, leucine, isoleucine, and lysine. Experimental evidence has shown that mutation of the Gln202 residue results in a decrease in the enzymatic activity, thus suggesting the main role of the carboligation cat...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00863
更新日期：2020-02-24 00:00:00
abstract：:Prediction of compound properties from structure via quantitative structure-activity relationship and machine-learning approaches is an important computational chemistry task in small-molecule drug research. Though many such properties are dependent on three-dimensional structures or even conformer ensembles, the majo...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00151
更新日期：2018-05-29 00:00:00
abstract：:In a departure from conventional chemical approaches, data-driven models of chemical reactions have recently been shown to be statistically successful using machine learning. These models, however, are largely black box in character and have not provided the kind of chemical insights that historically advanced the fie...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00721
更新日期：2020-03-23 00:00:00
abstract：:Development of coarse-grained (CG) molecular dynamics models is often a laborious process which commonly relies upon approximations to similar models, rather than systematic parametrization. PyCGTOOL automates much of the construction of CG models via calculation of both equilibrium values and force constants of inter...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00096
更新日期：2017-04-24 00:00:00
abstract：:The protection exerted by 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), a phenolic compound recently isolated from the Pacific oyster, against oxidative stress (OS) is investigated using the density functional theory. Our results indicate that DHMBA is an outstanding peroxyl radical scavenger, being about 15 times an...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00513
更新日期：2015-12-28 00:00:00
abstract：:The large volume of protein-ligand structures now available enables innovative and efficient protocols in computational FBDD (Fragment-Based Drug Design) to be proposed based on experimental data. In this work, we build a database of MED-Portions, where a MED-Portion is a new structural object encoding protein-fragmen...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci8003094
更新日期：2009-02-01 00:00:00
abstract：:We examine the sensitivity of folding molecular dynamics simulations on the choice between three variants of the same force field (the AMBER99SB force field and its ILDN, NMR-ILDN, and STAR-ILDN variants). Using two different peptide systems (a marginally stable helical peptide and a β-hairpin) and a grand total of mo...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00493
更新日期：2016-10-24 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
abstract：:We describe a novel deep learning neural network method and its application to impute assay pIC50 values. Unlike conventional machine learning approaches, this method is trained on sparse bioactivity data as input, typical of that found in public and commercial databases, enabling it to learn directly from correlation...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00768
更新日期：2019-03-25 00:00:00
abstract：:Membrane-bound protein receptors are a primary biological drug target, but the computational analysis of membrane proteins has been limited. In order to improve molecular mechanics Poisson-Boltzmann surface area (MMPBSA) binding free energy calculations for membrane protein-ligand systems, we have optimized a new hete...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00363
更新日期：2019-06-24 00:00:00
abstract：:The knowledge of the capacity of a data set to be modeled in the first stages of the building of quantitative structure-activity relationship (QSAR) prediction models is an important issue because it might reduce the effort and time necessary to select or reject data sets and in refining the data set's composition. Th...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00188
更新日期：2018-09-24 00:00:00
abstract：:All molecules of up to 11 atoms of C, N, O, and F possible under consideration of simple valency, chemical stability, and synthetic feasibility rules were generated and collected in a database (GDB). GDB contains 26.4 million molecules (110.9 million stereoisomers), including three- and four-membered rings and triple ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci600423u
更新日期：2007-03-01 00:00:00
abstract：:Telomere maintenance is a universal cancer hallmark, and small molecules that disrupt telomere maintenance generally have anticancer properties. Since the vast majority of cancer cells utilize telomerase activity for telomere maintenance, the enzyme has been considered as an anticancer drug target. Recently, rational ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00336
更新日期：2015-12-28 00:00:00
abstract：:Standardization is used to ensure that the variables in a similarity calculation make an equal contribution to the computed similarity value. This paper compares the use of seven different methods that have been suggested previously for the standardization of integer-valued or real-valued data, comparing the results w...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800224h
更新日期：2009-02-01 00:00:00
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：:With chemical libraries increasingly containing millions of compounds or more, there is a fast-growing need for computational methods that can rank or prioritize compounds for screening. Machine learning methods have shown considerable promise for this task; indeed, classification methods such as support vector machin...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci9003865
更新日期：2010-05-24 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：:Drug-induced torsade de pointes (TdP) is a life-threatening ventricular arrhythmia responsible for the withdrawal of many drugs from the market. Although currently used TdP risk-assessment methods are effective, they are expensive and prone to produce false positives. In recent years, in silico cardiac simulations hav...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00201
更新日期：2020-10-26 00:00:00
abstract：:Grass weed populations resistant to acetyl-CoA carboxylase-inhibiting (ACCase; EC 6.4.1.2) herbicides represent a major problem for the sustainable development of modern agriculture. In the present study, extensive computational simulations, including homology modeling, molecular dynamics (MD) simulations, and molecul...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci900174d
更新日期：2009-08-01 00:00:00
abstract：:We report here on long-time all-atomistic molecular dynamics simulations of functional supramolecular nanotubes composed by the self-assembly of peptide-drug amphiphiles (DAs). These DAs have been shown to possess an inherently high drug loading of the hydrophobic anticancer drug camptothecin. We probe the self-assemb...
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
abstract：:The appropriate selection of a chemical space represented by the data set, the selection of its chemical data representation, the development of a correct modeling process using a robust and reproducible algorithm, and the performance of an exhaustive training and external validation determine the usability and reprod...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00492
更新日期：2017-11-27 00:00:00
