Abstract:
:Molecular docking can account for receptor flexibility by combining the docking score over multiple rigid receptor conformations, such as snapshots from a molecular dynamics simulation. Here, we evaluate a number of common snapshot selection strategies using a quality metric from stratified sampling, the efficiency of stratification, which compares the variance of a selection strategy to simple random sampling. We also extend the metric to estimators of exponential averages (which involve an exponential transformation, averaging, and inverse transformation) and minima. For docking sets of over 500 ligands to four different proteins of varying flexibility, we observe that, for estimating ensemble averages and exponential averages, many clustering algorithms have similar performance trends: for a few snapshots (less than 25), medoids are the most efficient, while, for a larger number, optimal (the allocation that minimizes the variance) and proportional (to the size of each cluster) allocation become more efficient. Proportional allocation appears to be the most consistently efficient for estimating minima.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Xie B,Clark JD,Minh DDLdoi
10.1021/acs.jcim.8b00314subject
Has Abstractpub_date
2018-09-24 00:00:00pages
1915-1925issue
9eissn
1549-9596issn
1549-960Xjournal_volume
58pub_type
杂志文章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::Modern industrial lubricants are often blended with an assortment of chemical additives to improve the performance of the base stock. Machine learning-based predictive models allow fast and veracious derivation of material properties and facilitate novel and innovative material designs. In this study, we outline the d...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b01068
更新日期:2020-03-23 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 number of journal articles in the scientific domain has grown to the point where it has become impossible for researchers to capitalize on all findings in their relevant discipline. Information is stored in these articles in a number of ways, including figures that describe important results. In organic chemistry,...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00042
更新日期:2020-04-27 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::We report the development of homology models of dopamine (D(2), D(3), and D(4)), serotonin (5-HT(1B), 5-HT(2A), 5-HT(2B), and 5-HT(2C)), histamine (H(1)), and muscarinic (M(1)) receptors, based on the high-resolution structure of the beta(2)-adrenergic receptor. The homology models were built and refined using Prime. ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci900444q
更新日期:2010-04-26 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 Common Instrument Middleware Architecture (CIMA) aims at Grid-enabling a wide range of scientific instruments and sensors to enable easy access to and sharing and storage of data produced by these instruments and sensors. This paper describes the implementation of CIMA applied to the field of single-crystal X-ray ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci050368l
更新日期:2006-05-01 00:00:00
abstract::The protonation states for nucleic acid bases are difficult to assess experimentally. In the context of DNA triplex, the protonation state of cytidine in the third strand is particularly important, because it needs to be protonated in order to form Hoogsteen hydrogen bonds. A sugar modification, locked nucleic acid (L...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00741
更新日期:2018-04-23 00:00:00
abstract::To discover non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) that are effective against both wild-type (WT) virus and variants that encode the clinically troublesome Tyr181Cys (Y181C) RT mutation, virtual screening by docking was carried out using three RT structures and more than 2 million commercial...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci900068k
更新日期:2009-05-01 00:00:00
abstract::The ligand binding determinants for the angiotensin II type 1 receptor (AT1R), a G protein-coupled receptor (GPCR), have been characterized by means of computer simulations. As a first step, a pharmacophore model of various known AT1R ligands exhibiting a wide range of binding affinities was generated. Second, a struc...
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::An accurate scoring function is expected to correctly select the most stable structure from a set of pose candidates. One can hypothesize that a scoring function's ability to identify the most stable structure might be improved by emphasizing the most relevant atom pairwise interactions. However, it is hard to evaluat...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00356
更新日期:2019-07-22 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::The interaction between small molecules and proteins is one of the major concerns for structure-based drug design because the principles of protein-ligand interactions and molecular recognition are not thoroughly understood. Fortunately, the analysis of protein-ligand complexes in the Protein Data Bank (PDB) enables u...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci100386y
更新日期:2011-04-25 00:00:00
abstract::Flavonoids, the vastest class of natural polyphenols, are extensively investigated for their multiple benefits on human health. Due to their physicochemical or biological properties, many representatives are considered to exhibit low selectivity among various protein targets or to plague high-throughput screening (HTS...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci5002668
更新日期:2014-08-25 00:00:00
abstract::Ergotamine (ERG) and dihydroergotamine (DHE), common migraine drugs, have small structural differences but lead to clinically important distinctions in their pharmacological profiles. For example, DHE is less potent than ERG by about 10-fold at the 5-hydroxytrptamine receptor 1B (5-HT1B). Although the high-resolution ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b01082
更新日期:2020-03-23 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::A compound's synthetic accessibility (SA) is an important aspect of drug design, since in some cases computer-designed compounds cannot be synthesized. There have been several reports on SA prediction, most of which have focused on the difficulties of synthetic reactions based on retro-synthesis analyses, reaction dat...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci500568d
更新日期:2014-12-22 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::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::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::The d-Ala:d-Lac ligase, VanA, plays a critical role in the resistance of vancomycin. Indeed, it is involved in the synthesis of a peptidoglycan precursor, to which vancomycin cannot bind. The reaction catalyzed by VanA requires the opening of the so-called "ω-loop", so that the substrates can enter the active site. He...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.6b00211
更新日期:2016-09-26 00:00:00
abstract::FFAR4 has been considered as a potential target for metabolic diseases, including diabetes. Some compounds with biphenyl scaffold, represented by compound SR13 reported by our group, showed significant FFAR4 selectivity. However, the molecular basis for their selectivity has not been definitely disclosed. This study p...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00735
更新日期:2019-10-28 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::It is of great interest in modern drug design to accurately calculate the free energies of protein-ligand or nucleic acid-ligand binding. MM-PBSA (molecular mechanics Poisson-Boltzmann surface area) and MM-GBSA (molecular mechanics generalized Born surface area) have gained popularity in this field. For both methods, ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300064d
更新日期:2012-05-25 00:00:00
abstract::Class II fructose-1,6-bisphosphate aldolases (FBA-II) are attractive new targets for the discovery of drugs to combat invasive fungal infection, because they are absent in animals and higher plants. Although several FBA-II inhibitors have been reported, none of these inhibitors exhibit antifungal effect so far. In thi...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.6b00763
更新日期:2017-06-26 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::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::Protein-protein interactions (PPIs) play vital roles in regulating biological processes, such as cellular and signaling pathways. Hotspots are certain residues located at protein-protein interfaces that contribute more in protein-protein binding than other residues. Research on the mutational effects of hotspots is im...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00966
更新日期:2021-01-25 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