GPCR-Bench: A Benchmarking Set and Practitioners' Guide for G Protein-Coupled Receptor Docking.

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 publically available docking benchmarking set in the spirit of the DUD and DUD-E reference data sets for validation studies, containing 25 nonredundant high-resolution GPCR costructures with an accompanying set of diverse ligands and computational decoy molecules for each target. Benchmarking sets are often used to compare docking protocols; however, it is important to evaluate docking methods not by "retrospective" hit rates but by the actual likelihood that they will produce novel prospective hits. Therefore, docking protocols must not only rank active molecules highly but also produce good poses that a chemist will select for purchase and screening. Currently, no simple objective machine-scriptable function exists that can do this; instead, docking hit lists must be subjectively examined in a consistent way to compare between docking methods. We present here a case study highlighting considerations we feel are of importance when evaluating a method, intended to be useful as a practitioners' guide.

journal_name

J Chem Inf Model

authors

Weiss DR,Bortolato A,Tehan B,Mason JS

doi

10.1021/acs.jcim.5b00660

subject

Has Abstract

pub_date

2016-04-25 00:00:00

pages

642-51

issue

4

eissn

1549-9596

issn

1549-960X

journal_volume

56

pub_type

杂志文章
  • Similarity searching in databases of flexible 3D structures using autocorrelation vectors derived from smoothed bounded distance matrices.

    abstract::This paper presents an exploratory study of a novel method for flexible 3-D similarity searching based on autocorrelation vectors and smoothed bounded distance matrices. Although the new approach is unable to outperform an existing 2-D similarity searching in terms of enrichment factors, it is able to retrieve differe...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci0503863

    authors: Rhodes N,Clark DE,Willett P

    更新日期:2006-03-01 00:00:00

  • Simulation-Based Algorithm for Two-Dimensional Chemical Structure Diagram Generation of Complex Molecules and Ligand-Protein Interactions.

    abstract::Computer programs for structure diagram generation (SDG) are indispensable cheminformatic tools that translate one- or three-dimensional (1D or 3D) chemical structure data stored in electronic formats to human-readable 2D depictions. Although many such programs are known, only a moderate part of chemical space can be ...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.6b00391

    authors: Frączek T

    更新日期:2016-12-27 00:00:00

  • A Coarse-Grained Force Field Parameterized for MgCl2 and CaCl2 Aqueous Solutions.

    abstract::Calcium and magnesium ions play important roles in many physicochemical processes. To facilitate the investigation of phenomena related to these ions that occur over large length and time scales, a coarse-grained force field (CGFF) is developed for MgCl2 and CaCl2 aqueous solutions. The ions are modeled by CG beads wi...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.7b00206

    authors: Gong Z,Sun H

    更新日期:2017-07-24 00:00:00

  • Discovery and Evaluation of Anti-Fibrinolytic Plasmin Inhibitors Derived from 5-(4-Piperidyl)isoxazol-3-ol (4-PIOL).

    abstract::Inhibition of plasmin has been found to effectively reduce fibrinolysis and to avoid hemorrhage. This can be achieved by addressing its kringle 1 domain with the known drug and lysine analogue tranexamic acid. Guided by shape similarities toward a previously discovered lead compound, 5-(4-piperidyl)isoxazol-3-ol, a se...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.7b00255

    authors: Schmidt TC,Eriksson PO,Gustafsson D,Cosgrove D,Frølund B,Boström J

    更新日期:2017-07-24 00:00:00

  • Computational Design of Biologically Active Anticancer Peptides and Their Interactions with Heterogeneous POPC/POPS Lipid Membranes.

    abstract::Over the last few decades, anticancer peptides (ACPs) have turned into potential warheads against cancer. Apart from small molecules and monoclonal antibodies, ACPs have been proven to be effective against cancer cells. ACPs are small cationic peptides that selectively bind to the negatively charged cancer cell membra...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.9b00348

    authors: Singh M,Kumar V,Sikka K,Thakur R,Harioudh MK,Mishra DP,Ghosh JK,Siddiqi MI

    更新日期:2020-01-27 00:00:00

  • Statistical confidence for variable selection in QSAR models via Monte Carlo cross-validation.

    abstract::A new variable selection wrapper method named the Monte Carlo variable selection (MCVS) method was developed utilizing the framework of the Monte Carlo cross-validation (MCCV) approach. The MCVS method reports the variable selection results in the most conventional and common measure of statistical hypothesis testing,...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci700283s

    authors: Konovalov DA,Sim N,Deconinck E,Vander Heyden Y,Coomans D

    更新日期:2008-02-01 00:00:00

  • Underestimated Halogen Bonds Forming with Protein Backbone in Protein Data Bank.

    abstract::Halogen bonds (XBs) are attracting increasing attention in biological systems. Protein Data Bank (PDB) archives experimentally determined XBs in biological macromolecules. However, no software for structure refinement in X-ray crystallography takes into account XBs, which might result in the weakening or even vanishin...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.7b00235

    authors: Zhang Q,Xu Z,Shi J,Zhu W

    更新日期:2017-07-24 00:00:00

  • Affinity and Selectivity Assessment of Covalent Inhibitors by Free Energy Calculations.

    abstract::Covalent inhibitors have been gaining increased attention in drug discovery due to their beneficial properties such as long residence time, high biochemical efficiency, and specificity. Optimization of covalent inhibitors is a complex task that involves parallel monitoring of the noncovalent recognition elements and t...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.0c00834

    authors: Mihalovits LM,Ferenczy GG,Keserű GM

    更新日期:2020-12-28 00:00:00

  • Antihypertensive drug valsartan in solution and at the AT1 receptor: conformational analysis, dynamic NMR spectroscopy, in silico docking, and molecular dynamics simulations.

    abstract::The conformational properties of AT1 antagonist valsartan have been analyzed both in solution and at the binding site of the receptor. Low energy conformations of valsartan in solution were explored by NMR spectroscopy and molecular modeling studies. The NMR results showed the existence of two distinct and almost isoe...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci800427s

    authors: Potamitis C,Zervou M,Katsiaras V,Zoumpoulakis P,Durdagi S,Papadopoulos MG,Hayes JM,Grdadolnik SG,Kyrikou I,Argyropoulos D,Vatougia G,Mavromoustakos T

    更新日期:2009-03-01 00:00:00

  • Novel inhibitors of human histone deacetylase (HDAC) identified by QSAR modeling of known inhibitors, virtual screening, and experimental validation.

    abstract::Inhibitors of histone deacetylases (HDACIs) have emerged as a new class of drugs for the treatment of human cancers and other diseases because of their effects on cell growth, differentiation, and apoptosis. In this study we have developed several quantitative structure-activity relationship (QSAR) models for 59 chemi...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci800366f

    authors: Tang H,Wang XS,Huang XP,Roth BL,Butler KV,Kozikowski AP,Jung M,Tropsha A

    更新日期:2009-02-01 00:00:00

  • Efficient Strategy for the Calculation of Solvation Free Energies in Water and Chloroform at the Quantum Mechanical/Molecular Mechanical Level.

    abstract::The partitioning of solute molecules between immiscible solvents with significantly different polarities is of great importance. The polarization between the solute and solvent molecules plays an essential role in determining the solubility of the solute, which makes computational studies utilizing molecular mechanics...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.7b00001

    authors: Wang M,Li P,Jia X,Liu W,Shao Y,Hu W,Zheng J,Brooks BR,Mei Y

    更新日期:2017-10-23 00:00:00

  • Heuristics from Modeling of Spectral Overlap in Förster Resonance Energy Transfer (FRET).

    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

    authors: Qi Q,Taniguchi M,Lindsey JS

    更新日期:2019-02-25 00:00:00

  • Novel Consensus Architecture To Improve Performance of Large-Scale Multitask Deep Learning QSAR Models.

    abstract::Advances in the development of high-throughput screening and automated chemistry have rapidly accelerated the production of chemical and biological data, much of them freely accessible through literature aggregator services such as ChEMBL and PubChem. Here, we explore how to use this comprehensive mapping of chemical ...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.9b00526

    authors: Zakharov AV,Zhao T,Nguyen DT,Peryea T,Sheils T,Yasgar A,Huang R,Southall N,Simeonov A

    更新日期:2019-11-25 00:00:00

  • Parameterization and conformational sampling effects in pharmacophore multiplet searching.

    abstract::Pharmacophore patterns in ligands can be effectively characterized in terms of their constituent pharmacophore multiplets. Bitsets (fingerprints) encoding which particular multiplets are found in a given ligand have been and continue to be used as molecular descriptors in a range of molecular modeling applications, fr...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci800234q

    authors: Fox PC,Wolohan PR,Abrahamian E,Clark RD

    更新日期:2008-12-01 00:00:00

  • Ranking Reversible Covalent Drugs: From Free Energy Perturbation to Fragment Docking.

    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

    authors: Zhang H,Jiang W,Chatterjee P,Luo Y

    更新日期:2019-05-28 00:00:00

  • Leave-cluster-out cross-validation is appropriate for scoring functions derived from diverse protein data sets.

    abstract::With the emergence of large collections of protein-ligand complexes complemented by binding data, as found in PDBbind or BindingMOAD, new opportunities for parametrizing and evaluating scoring functions have arisen. With huge data collections available, it becomes feasible to fit scoring functions in a QSAR style, i.e...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci100264e

    authors: Kramer C,Gedeck P

    更新日期:2010-11-22 00:00:00

  • Discovery of New SIRT2 Inhibitors by Utilizing a Consensus Docking/Scoring Strategy and Structure-Activity Relationship Analysis.

    abstract::SIRT2, which is a NAD+ (nicotinamide adenine dinucleotide) dependent deacetylase, has been demonstrated to play an important role in the occurrence and development of a variety of diseases such as cancer, ischemia-reperfusion, and neurodegenerative diseases. Small molecule inhibitors of SIRT2 are thought to be potenti...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.6b00714

    authors: Huang S,Song C,Wang X,Zhang G,Wang Y,Jiang X,Sun Q,Huang L,Xiang R,Hu Y,Li L,Yang S

    更新日期:2017-04-24 00:00:00

  • Transplant-insert-constrain-relax-assemble (TICRA): protein-ligand complex structure modeling and application to kinases.

    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...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci100256u

    authors: Meshkat S,Klon AE,Zou J,Wiseman JS,Konteatis Z

    更新日期:2011-01-24 00:00:00

  • Effects of Ligand Environment in Zr(IV) Assisted Peptide Hydrolysis.

    abstract::In this DFT study, activities of 11 different N2O4, N2O3, and NO2 core containing Zr(IV) complexes, 4,13-diaza-18-crown-6 (I'N2O4), 1,4,10-trioxa-7,13-diazacyclopentadecane (I'N2O3), and 2-(2-methoxy)ethanol (I'NO2), respectively, and their analogues in peptide hydrolysis have been investigated. Based on the experimen...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.6b00781

    authors: Zhang T,Sharma G,Paul TJ,Hoffmann Z,Prabhakar R

    更新日期:2017-05-22 00:00:00

  • Similarity perception of reactions catalyzed by oxidoreductases and hydrolases using different classification methods.

    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

    authors: Hu X,Yan A,Tan T,Sacher O,Gasteiger J

    更新日期:2010-06-28 00:00:00

  • Relationships between Molecular Complexity, Biological Activity, and Structural Diversity.

    abstract::Following the theoretical model by Hann et al. moderately complex structures are preferable lead compounds since they lead to specific binding events involving the complete ligand molecule. To make this concept usable in practice for library design, we studied several complexity measures on the biological activity of ...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci0503558

    authors: Schuffenhauer A,Brown N,Selzer P,Ertl P,Jacoby E

    更新日期:2006-03-01 00:00:00

  • Modeling p K Shift in DNA Triplexes Containing Locked Nucleic Acids.

    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

    authors: Hartono YD,Xu Y,Karshikoff A,Nilsson L,Villa A

    更新日期:2018-04-23 00:00:00

  • Automated extraction of information on chemical-P-glycoprotein interactions from the literature.

    abstract::Knowledge of the interactions between drugs and transporters is important for drug discovery and development as well as for the evaluation of their clinical safety. We recently developed a text-mining system for the automatic extraction of information on chemical-CYP3A4 interactions from the literature. This system is...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci4003188

    authors: Yoshida S,Yamashita F,Ose A,Maeda K,Sugiyama Y,Hashida M

    更新日期:2013-10-28 00:00:00

  • Structure-based approach for the study of estrogen receptor binding affinity and subtype selectivity.

    abstract::Estrogens exert important physiological effects through the modulation of two human estrogen receptor (hER) subtypes, alpha (hERalpha) and beta (hERbeta). Because the levels and relative proportion of hERalpha and hERbeta differ significantly in different target cells, selective hER ligands could target specific tissu...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci8002182

    authors: Salum LB,Polikarpov I,Andricopulo AD

    更新日期:2008-11-01 00:00:00

  • Computational Insight Into the Mechanism of SARS-CoV-2 Membrane Fusion.

    abstract::Membrane fusion, a key step in the early stages of virus propagation, allows the release of the viral genome in the host cell cytoplasm. The process is initiated by fusion peptides that are small, hydrophobic components of viral membrane-embedded glycoproteins and are typically conserved within virus families. Here, w...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.0c01231

    authors: Borkotoky S,Dey D,Banerjee M

    更新日期:2021-01-25 00:00:00

  • In silico analysis of the thermodynamic stability changes of psychrophilic and mesophilic alpha-amylases upon exhaustive single-site mutations.

    abstract::Identifying sequence modifications that distinguish psychrophilic from mesophilic proteins is important for designing enzymes with different thermodynamic stabilities and to understand the underlying mechanisms. The PoPMuSiC algorithm is used to introduce, in silico, all the single-site mutations in four mesophilic an...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci050473v

    authors: Gilis D

    更新日期:2006-05-01 00:00:00

  • Molecular Mechanism, Dynamics, and Energetics of Protein-Mediated Dinucleotide Flipping in a Mismatched DNA: A Computational Study of the RAD4-DNA Complex.

    abstract::DNA damage alters genetic information and adversely affects gene expression pathways leading to various complex genetic disorders and cancers. DNA repair proteins recognize and rectify DNA damage and mismatches with high fidelity. A critical molecular event that occurs during most protein-mediated DNA repair processes...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.7b00636

    authors: Pitta K,Krishnan M

    更新日期:2018-03-26 00:00:00

  • Searching for coordinated activity cliffs using particle swarm optimization.

    abstract::Activity cliffs are formed by structurally similar compounds having large potency differences. Coordinated activity cliffs evolve when compounds within groups of structural neighbors form multiple cliffs with different partners, giving rise to local networks of cliffs in a data set. Using particle swarm optimization, ...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci3000503

    authors: Namasivayam V,Bajorath J

    更新日期:2012-04-23 00:00:00

  • ReFlex3D: Refined Flexible Alignment of Molecules Using Shape and Electrostatics.

    abstract::We present an algorithm, ReFlex3D, for the refinement of flexible molecular alignments based on their three-dimensional shape and electrostatic properties. The algorithm is designed to be used with fast conformer generators to refine an initial overlay between two molecules and thus to obtain improved overlaps as judg...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.7b00618

    authors: Schmidt TC,Cosgrove DA,Boström J

    更新日期:2018-04-23 00:00:00

  • T-Cell Receptor Binding Affects the Dynamics of the Peptide/MHC-I Complex.

    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

    authors: Knapp B,Deane CM

    更新日期:2016-01-25 00:00:00