Interpretation of the binding affinities of PTP1B inhibitors with the MM-GB/SA method and the X-score scoring function.

Abstract:

:We have studied the binding affinities of a set of 45 small-molecule inhibitors to protein tyrosine phosphatase 1B (PTP1B) through computational approaches. All of these compounds share a common oxalylamino benzoic acid (OBA) moiety. The complex structure of each compound was modeled by using the GOLD program plus the ASP scoring function. Each complex structure was then subjected to a molecular dynamics (MD) simulation of 2 ns long by using the AMBER program. Based on the configurational ensembles retrieved from MD trajectories, both MM-GB/SA and MM-PB/SA were employed to compute the binding free energies of all 45 PTP1B inhibitors. The correlation coefficient between the MM-GB/SA results and experimental binding data was 0.87 and the standard deviation was 0.60 kcal/mol. The performance of MM-PB/SA was slightly inferior to that of MM-GB/SA. Several aspects of the MM-GB(PB)/SA method were explored in our study to obtain optimized results. The X-Score scoring function was found to produce equally good results as MM-GB/SA on both the complex structures prepared by molecular docking and the configurational ensembles obtained through lengthy MD simulations. The structure-activity relationship of this set of compounds is also discussed based on the computed results. The computational approaches validated in our study are hopefully applicable to the study of other classes of PTP1B inhibitors.

journal_name

J Chem Inf Model

authors

Zhang X,Li X,Wang R

doi

10.1021/ci8004429

subject

Has Abstract

pub_date

2009-04-01 00:00:00

pages

1033-48

issue

4

eissn

1549-9596

issn

1549-960X

journal_volume

49

pub_type

杂志文章
  • Molecular Self-Assembly Strategy for Encapsulation of an Amphipathic α-Helical Antimicrobial Peptide into the Different Polymeric and Copolymeric Nanoparticles.

    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

    authors: Jafari M,Doustdar F,Mehrnejad F

    更新日期:2019-01-28 00:00:00

  • Multitarget structure-activity relationships characterized by activity-difference maps and consensus similarity measure.

    abstract::Dual and triple activity-difference (DAD/TAD) maps are tools for the systematic characterization of structure-activity relationships (SAR) of compound data sets screened against two or three targets. DAD and TAD maps are two- and three- dimensional representations of the pairwise activity differences of compound data ...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci200281v

    authors: Medina-Franco JL,Yongye AB,Pérez-Villanueva J,Houghten RA,Martínez-Mayorga K

    更新日期:2011-09-26 00:00:00

  • Systematics of high-genus fullerenes.

    abstract::In this article, we present a systematic way to classify a family of high-genus fullerenes (HGFs) by decomposing them into two types of necklike structures, which are the negatively curved parts of parent toroidal carbon nanotubes. By replacing the faces of a uniform polyhedron with these necks, an HGF polyhedron corr...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci9001124

    authors: Chuang C,Jin BY

    更新日期:2009-07-01 00:00:00

  • Pharmacophore-based virtual screening and experimental validation of novel inhibitors against cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphosphatase.

    abstract::Cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphoshatase (cy-FBP/SBPase) is a potential enzymatic target for screening of novel inhibitors that can combat harmful algal blooms. In the present study, we targeted the substrate binding pocket of cy-FBP/SBPase. A series of novel hit compounds from the SPECs database w...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci4007529

    authors: Sun Y,Zhang R,Li D,Feng L,Wu D,Feng L,Huang P,Ren Y,Feng J,Xiao S,Wan J

    更新日期:2014-03-24 00:00:00

  • Template CoMFA: the 3D-QSAR Grail?

    abstract::Template CoMFA, a novel alignment methodology for training or test set structures in 3D-QSAR, is introduced. Its two most significant advantages are its complete automation and its ability to derive a single combined model from multiple structural series affecting a biological target. Its only two inputs are one or mo...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci400696v

    authors: Cramer RD,Wendt B

    更新日期:2014-02-24 00:00:00

  • The molecular basis for the selectivity of tadalafil toward phosphodiesterase 5 and 6: a modeling study.

    abstract::Great attention has been paid to the clinical significance of phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil, tadalafil, and vardenafil widely used for erectile dysfunction. However, sildenafil causes side effects on visual functions since it shows similar potencies to inhibit PDE5 and PDE6, whereas tadalaf...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci400458z

    authors: Huang YY,Li Z,Cai YH,Feng LJ,Wu Y,Li X,Luo HB

    更新日期:2013-11-25 00:00:00

  • Modeling compound-target interaction network of traditional Chinese medicines for type II diabetes mellitus: insight for polypharmacology and drug design.

    abstract::In this study, in order to elucidate the action mechanism of traditional Chinese medicines (TCMs) that exhibit clinical efficacy for type II diabetes mellitus (T2DM), an integrated protocol that combines molecular docking and pharmacophore mapping was employed to find the potential inhibitors from TCM for the T2DM-rel...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci400146u

    authors: Tian S,Li Y,Li D,Xu X,Wang J,Zhang Q,Hou T

    更新日期:2013-07-22 00:00:00

  • OPUS-Rota3: Improving Protein Side-Chain Modeling by Deep Neural Networks and Ensemble Methods.

    abstract::Side-chain modeling is critical for protein structure prediction since the uniqueness of the protein structure is largely determined by its side-chain packing conformation. In this paper, differing from most approaches that rely on rotamer library sampling, we first propose a novel side-chain rotamer prediction method...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.0c00951

    authors: Xu G,Wang Q,Ma J

    更新日期:2020-12-28 00:00:00

  • Standardizing and simplifying analysis of peptide library data.

    abstract::Peptide libraries allow researchers to quickly find hundreds of peptide sequences with a desired property. Currently, the large amount of data generated from peptide libraries is analyzed by hand, where researchers search for repeating patterns in the peptide sequences. Such patterns are called motifs. In this work, w...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci300484q

    authors: White AD,Keefe AJ,Nowinski AK,Shao Q,Caldwell K,Jiang S

    更新日期:2013-02-25 00:00:00

  • Informatics-Aided Density Functional Theory Study on the Li Ion Transport of Tavorite-Type LiMTO4F (M(3+)-T(5+), M(2+)-T(6+)).

    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

    authors: Jalem R,Kimura M,Nakayama M,Kasuga T

    更新日期:2015-06-22 00:00:00

  • In silico deconstruction of ATP-competitive inhibitors of glycogen synthase kinase-3β.

    abstract::Fragment-based methods have emerged in the last two decades as alternatives to traditional high throughput screenings for the identification of chemical starting points in drug discovery. One arguable yet popular assumption about fragment-based design is that the fragment binding mode remains conserved upon chemical e...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci300355p

    authors: Bisignano P,Lambruschini C,Bicego M,Murino V,Favia AD,Cavalli A

    更新日期:2012-12-21 00:00:00

  • Accurate Estimation of pKb Values for Amino Groups from Surface Electrostatic Potential (VS,min) Calculations: The Isoelectric Points of Amino Acids as a Case Study.

    abstract::Theoretical calculation of equilibrium dissociation constants is a very computationally demanding and time-consuming process since it requires an extremely accurate computation of the solvation free energy changes for each of the species involved. By correlating the minimum surface electrostatic potential (VS,min) on ...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.9b01173

    authors: Sandoval-Lira J,Mondragón-Solórzano G,Lugo-Fuentes LI,Barroso-Flores J

    更新日期:2020-03-23 00:00:00

  • 3D QSAR methods: Phase and Catalyst compared.

    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

    authors: Evans DA,Doman TN,Thorner DA,Bodkin MJ

    更新日期:2007-05-01 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

  • 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

  • Evaluating Unexpectedly Short Non-covalent Distances in X-ray Crystal Structures of Proteins with Electronic Structure Analysis.

    abstract::We investigate unexpectedly short non-covalent distances (<85% of the sum of van der Waals radii) in X-ray crystal structures of proteins. We curate over 11 000 high-quality protein crystal structures and an ultra-high-resolution (1.2 Å or better) subset containing >900 structures. Although our non-covalent distance c...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.9b00144

    authors: Qi HW,Kulik HJ

    更新日期:2019-05-28 00:00:00

  • Role of water in ligand binding to maltose-binding protein: insight from a new docking protocol based on the 3D-RISM-KH molecular theory of solvation.

    abstract::Maltose-binding protein is a periplasmic binding protein responsible for transport of maltooligosaccarides through the periplasmic space of Gram-negative bacteria, as a part of the ABC transport system. The molecular mechanisms of the initial ligand binding and induced large scale motion of the protein's domains still...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci500520q

    authors: Huang W,Blinov N,Wishart DS,Kovalenko A

    更新日期:2015-02-23 00:00:00

  • Combined approach using ligand efficiency, cross-docking, and antitarget hits for wild-type and drug-resistant Y181C HIV-1 reverse transcriptase.

    abstract::New hits against HIV-1 wild-type and Y181C drug-resistant reverse transcriptases were predicted taking into account the possibility of some of the known metabolism interactions. In silico hits against a set of antitargets (i.e., proteins or nucleic acids that are off-targets from the desired pharmaceutical target obje...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci200203h

    authors: García-Sosa AT,Sild S,Takkis K,Maran U

    更新日期:2011-10-24 00:00:00

  • Conformator: A Novel Method for the Generation of Conformer Ensembles.

    abstract::Computer-aided drug design methods such as docking, pharmacophore searching, 3D database searching, and the creation of 3D-QSAR models need conformational ensembles to handle the flexibility of small molecules. Here, we present Conformator, an accurate and effective knowledge-based algorithm for generating conformer e...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.8b00704

    authors: Friedrich NO,Flachsenberg F,Meyder A,Sommer K,Kirchmair J,Rarey M

    更新日期:2019-02-25 00:00:00

  • Exploring inhibitor release pathways in histone deacetylases using random acceleration molecular dynamics simulations.

    abstract::Molecular channel exploration perseveres to be the prominent solution for eliciting structure and accessibility of active site and other internal spaces of macromolecules. The volume and silhouette characterization of these channels provides answers for the issues of substrate access and ligand swapping between the ob...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci200584f

    authors: Kalyaanamoorthy S,Chen YP

    更新日期:2012-02-27 00:00:00

  • Learning To Predict Reaction Conditions: Relationships between Solvent, Molecular Structure, and Catalyst.

    abstract::Reaction databases provide a great deal of useful information to assist planning of experiments but do not provide any interpretation or chemical concepts to accompany this information. In this work, reactions are labeled with experimental conditions, and network analysis shows that consistencies within clusters of da...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.9b00313

    authors: Walker E,Kammeraad J,Goetz J,Robo MT,Tewari A,Zimmerman PM

    更新日期:2019-09-23 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

  • Ligand coordinate analysis of SC-558 from the active site to the surface of COX-2: a molecular dynamics study.

    abstract::We have performed a ligand coordinate analysis to monitor the movement of the inhibitor SC-558 from the active site of the COX-2 protein to the exterior using molecular dynamics techniques. This study provides an insight into the intermolecular interactions formed by the ligand during this journey. The published cryst...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci050142i

    authors: Sai Ram KV,Rambabu G,Sarma JA,Desiraju GR

    更新日期:2006-07-01 00:00:00

  • Structural insight into the unique binding properties of pyridylethanol(phenylethyl)amine inhibitor in human CYP51.

    abstract::Sterol 14α-demethylase (CYP51) is the main drug target for the treatment of fungal infections. The discovery of new efficient fungal CYP51 inhibitors requires an understanding of the structural requirements for selectivity for the fungal over the human ortholog. In this study, a binding mode of the pyridylethanol(phen...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci500556k

    authors: Zelenko U,Hodošček M,Rozman D,Golič Grdadolnik S

    更新日期:2014-12-22 00:00:00

  • RDChiral: An RDKit Wrapper for Handling Stereochemistry in Retrosynthetic Template Extraction and Application.

    abstract::There is a renewed interest in computer-aided synthesis planning, where the vast majority of approaches require the application of retrosynthetic reaction templates. Here we introduce RDChiral, an open-source Python wrapper for RDKit designed to provide consistent handling of stereochemical information in applying ret...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.9b00286

    authors: Coley CW,Green WH,Jensen KF

    更新日期:2019-06-24 00:00:00

  • Development of novel statistical potentials describing cation-pi interactions in proteins and comparison with semiempirical and quantum chemistry approaches.

    abstract::Novel statistical potentials derived from known protein structures are presented. They are designed to describe cation-pi and amino-pi interactions between a positively charged amino acid or an amino acid carrying a partially charged amino group and an aromatic moiety. These potentials are based on the propensity of r...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci050395b

    authors: Gilis D,Biot C,Buisine E,Dehouck Y,Rooman M

    更新日期:2006-03-01 00:00:00

  • Improved Computation of Protein-Protein Relative Binding Energies with the Nwat-MMGBSA Method.

    abstract::A MMGBSA variant (here referred to as Nwat-MMGBSA), based on the inclusion of a certain number of explicit water molecules (Nwat) during the calculations, has been tested on a set of 20 protein-protein complexes, using the correlation between predicted and experimental binding energy as the evaluation metric. Besides ...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.6b00196

    authors: Maffucci I,Contini A

    更新日期:2016-09-26 00:00:00

  • Molecular modeling of potential anticancer agents from African medicinal plants.

    abstract::Naturally occurring anticancer compounds represent about half of the chemotherapeutic drugs which have been put in the market against cancer until date. Computer-based or in silico virtual screening methods are often used in lead/hit discovery protocols. In this study, the "drug-likeness" of ~400 compounds from Africa...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci5003697

    authors: Ntie-Kang F,Nwodo JN,Ibezim A,Simoben CV,Karaman B,Ngwa VF,Sippl W,Adikwu MU,Mbaze LM

    更新日期:2014-09-22 00:00:00

  • Scores of extended connectivity fingerprint as descriptors in QSPR study of melting point and aqueous solubility.

    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

    doi:10.1021/ci800024c

    authors: Zhou D,Alelyunas Y,Liu R

    更新日期:2008-05-01 00:00:00

  • Benchmarking of Semiempirical Quantum-Mechanical Methods on Systems Relevant to Computer-Aided Drug Design.

    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...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.9b01171

    authors: Kříž K,Řezáč J

    更新日期:2020-03-23 00:00:00