Reliable structural information for rational design of benzoxazole type potential cholesteryl ester transfer protein (CETP) inhibitors through multiple validated modeling techniques.

Abstract:

:The drug design and discovery of lipid modulators is very demanding as no new molecule has entered into the market in the last 35 years. Cholesteryl ester transfer protein (CETP) is a promising target as lipid modulators. Inhibition of the CETP enzyme reduces the risk of cardiovascular events. The first CETP inhibitor torcetrapib and related drug candidates failed in the clinical trial due to the off-target effects leading to high toxicity. Thus, newer CETP inhibitors have now paramount importance to accelerate the drug discovery efforts in the field of cardiovascular disease (CVD). In the present study, 140 benzoxazole compounds were studied by using different chemometric techniques, for example, pharmacophore mapping, molecular docking, three-dimensional quantitative structure-activity relationship comparative molecular field analysis (3D-QSAR CoMFA), topomer CoMFA and Bayesian classification, in order to generate complete and reliable information regarding the structural requirements for the CETP inhibition. The best pharmacophore hypothesis was statistically significant (regression coefficient of 0.957 and a lower root mean square of 0.890). Molecular docking study revealed that cyano-substituted compounds form hydrogen bond with targeted macromolecule. The 3D-QSAR CoMFA model also produced a leave-one-out (LOO) cross-validated Q2 of 0.527, an R2 of 0.853 and an R2Pred of 0.603. Similarly, two topomer CoMFA models were also statistically significant and reliable in terms of their Q2, R2 and R2Pred values. The Bayesian classification study also provided the excellent ROC values of 0.919 and 0.939 for training and test sets, respectively. Overall, this study may help in the rational design of newer benzoxazole type compounds with higher CETP inhibition. Communicated by Ramaswamy H. Sarma.

journal_name

J Biomol Struct Dyn

authors

Amin SA,Adhikari N,Gayen S,Jha T

doi

10.1080/07391102.2018.1552895

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

4528-4541

issue

17

eissn

0739-1102

issn

1538-0254

journal_volume

37

pub_type

杂志文章
  • Discrimination between A-type and B-type conformations of double helical nucleic acid fragments in solution by means of two-dimensional nuclear Overhauser experiments.

    abstract::The solution structure of two double helical nucleic acid fragments, viz, r(CGCGCG) and d(CGCGCG), was probed by means of two-dimensional nuclear Overhauser effect spectroscopy. The two compounds were selected as models for the A-type and B-type double helical conformations, respectively, and it is shown that for each...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.1984.10507572

    authors: Haasnoot CA,Westerink HP,van der Marel GA,van Boom JH

    更新日期:1984-10-01 00:00:00

  • RUN-CBFbeta interaction in C. elegans: computational prediction and experimental verification.

    abstract::The Runt domain proteins are eukaryotic transcription factors that regulate major developmental pathways. All members of this family contain a highly-conserved sequence-specific DNA binding domain: the Runt domain (RD). Structural and biochemical studies have shown that the Runt domain undergoes a conformational trans...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2007.10507124

    authors: Suad O,Eyal E,Blumenzweig I,Kessler N,Levanon D,Groner Y,Shakked Z

    更新日期:2007-02-01 00:00:00

  • Effect of CTerm of human albumin on the aggregation propensity of Aβ1-42 peptide: a potential of mean force study.

    abstract::Alzheimer's disease (AD) is the most common progressive neurodegenerative brain disorder. It is characterized by the presence of extracellular aggregated fibrillary form of amyloid beta (Aβ) peptide and intraneuronal neurofibrillary tangles caused by the hyperphosphorylation of tau protein. Monomeric form of Aβ peptid...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2020.1730970

    authors: Dutta N,Borah P,Mattaparthi VSK

    更新日期:2020-03-02 00:00:00

  • Aqueous hydration of nucleic acid constituents: Monte Carlo computer simulation studies.

    abstract::Monte Carlo computer simulations were performed on dilute aqueous solutions of thymine, cytosine, uracil, adenine, guanine, the dimethyl phosphate anion in the gauche-gauche conformation and a ribose and deoxyribose derivative. The aqueous hydration of each molecule was analysed in terms of quasi-component distributio...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章,评审

    doi:10.1080/07391102.1984.10507565

    authors: Beveridge DL,Maye PV,Jayaram B,Ravishanker G,Mezei M

    更新日期:1984-10-01 00:00:00

  • Probing the dynamics between the substrate and the product towards glucose tolerance of Halothermothrix orenii β-glucosidase.

    abstract::Most β-Glucosidase (B8CYA8) are prone to inhibition by glucose. Experimentally observed specific activity of B8CYA8 on 20 mM, 50 mM, and 100 mM p-nitrophenyl-β-D-glucopyranoside (pNPGlc) substrate concentrations show surprise dependence on the presence of 0-3 M glucose at 335 K. We found that at high substrate concent...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2020.1796789

    authors: Konar S,Sinha SK,Datta S,Ghorai PK

    更新日期:2020-07-28 00:00:00

  • Electrostatics of Polymorphic DNA.

    abstract::The molecular electrostatic potential (MEP) and the molecular electrostatic field (MEF) are associated with significantly different patterns of distribution in the nucleic acids and their constituents. In particular, a) while the values of the minimal potentials at the reactive sites of the bases or at the phosphates ...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.1983.10507481

    authors: Pullman B

    更新日期:1983-12-01 00:00:00

  • Design, synthesis and biological evaluation of selected 3-[3-(amino) propoxy] benzenamines as acetylcholinesterase inhibitors.

    abstract::The present paper describes design, synthesis, and biological evaluation of a series of some 3-[3-(amino)propoxy]benzenamines as acetylcholinesterase inhibitors using mice as a model and piracetam as a reference drug. The structures of these compounds were confirmed by spectral analysis and compounds were tested for m...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2016.1220330

    authors: Malik R,Gupta R,Srivastava S,Choudhary BS,Sharma M

    更新日期:2017-08-01 00:00:00

  • Allowance for spatial dispersion of dielectric permittivity in polyelectrolyte model of DNA.

    abstract::In order to allow for real dielectric properties of a solvent in calculating of electrostatic characteristics of strongly charged polyions such as DNA in salt solution we consider a simple model of linear dielectric response of a medium. The interactions between charged particles are treated in the framework of self-c...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.1991.10507933

    authors: Lukashin AV,Beglov DB,Frank-Kamenetskii MD

    更新日期:1991-12-01 00:00:00

  • Solution structures of purine base analogues 6-chloroguanine, 8-azaguanine and allopurinol.

    abstract::Analogues of purine bases are highly relevant in the biological context and have been implicated as drug molecules for therapy against a number of diseases. Additionally, these molecules have been implicated to have a role in the prebiotic RNA world. However, experimental data on the structures of these molecules in a...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2012.745821

    authors: Gogia S,Puranik M

    更新日期:2014-01-01 00:00:00

  • Elucidation of molecular mechanism of stability of the heme-regulated eIF2α kinase upon binding of its ligand, hemin in its catalytic kinase domain.

    abstract::The eIF2α kinase activity of the heme-regulated inhibitor (HRI) is regulated by heme which makes it a unique member of the family of eIF2α kinases. Since heme concentrations create an equilibrium for the kinase to be active/inactive, it becomes important to study the heme binding effects upon the kinase and understand...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2017.1368417

    authors: Bhavnani V,Kaviraj S,Panigrahi P,Suresh CG,Yapara S,Pal J

    更新日期:2018-08-01 00:00:00

  • A note on crystal packing and global helix structure in short A-DNA duplexes.

    abstract::A simple relation exists between the packing density in crystals of short A-DNA duplexes and their global double-helical structure. The volume per nucleotide pair shows a linear inverse correlation with the mean displacement of base pairs from the best straight helix axis. The mean displacement is a measure of major g...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.1991.10507846

    authors: Heinemann U

    更新日期:1991-02-01 00:00:00

  • Structure-based drug repurposing for targeting Nsp9 replicase and spike proteins of severe acute respiratory syndrome coronavirus 2.

    abstract::Drug re-purposing might be a fast and efficient way of drug development against the novel coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We applied a bioinformatics approach using molecular dynamics and docking to identify FDA-approved drugs that can be re-purposed to ...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2020.1811773

    authors: Chandel V,Sharma PP,Raj S,Choudhari R,Rathi B,Kumar D

    更新日期:2020-08-24 00:00:00

  • Potency of inhibitors depends upon the accessibility of their aromatic rings within the hydrophobic specificity pocket: a novel avenue for future aldose reductase inhibitor design.

    abstract::Communicated by Ramaswamy H. Sarma. ...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 信件

    doi:10.1080/07391102.2020.1733090

    authors: Khan S,Somvanshi P,Singh A,Khan M,Mandal RK,Dar SA,Wahid M,Jawed A,Mishra BN,Haque S

    更新日期:2020-03-03 00:00:00

  • An insight to conserved water molecular dynamics of catalytic and structural Zn(+2) ions in matrix metalloproteinase 13 of human.

    abstract::Matrix Metalloproteinase (MMP)--13 or Collagenase--3 plays a significant role in the formation and remodeling of bone, tumor invasion and causes osteoarthritis. Water molecular dynamic studies of the five (1XUC, 1XUD, 1XUR, 456C, 830C) PDB and solvated structures of MMP-13 in human have been carried out upto 5 ns on a...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2011.10508591

    authors: Chakrabarti B,Bairagya HR,Mallik P,Mukhopadhyay BP,Bera A

    更新日期:2011-02-01 00:00:00

  • Structural and biological study of synthesized anthraquinone series of compounds with sulfonamide feature.

    abstract::1, 4 and 5, 8-Positions as well as type of functionalities on these positions at anthraquinone-9, 10-dione are proposed to be significant for anticancer activity. Therefore, keeping this into consideration, a series of 1-substituted anthraquinone-based compounds are designed, synthesized, characterized and biologicall...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2018.1552198

    authors: Awasthi P,Vatsal M,Sharma A

    更新日期:2019-10-01 00:00:00

  • The pathogenicity, structural and functional exploration of human HMGB1 single nucleotide polymorphisms using in silico study.

    abstract::The human HMGB1 gene mutations have a major impact on several immune-related diseases and cancer. The detrimental effect of non-synonymous mutations of HMGB1 has not been investigated yet, hence the present study aims to examine single nucleotide polymorphisms and their implications on the structure-function of human ...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2019.1682048

    authors: Santhiya P,Christian Bharathi A,Syed Ibrahim B

    更新日期:2020-09-01 00:00:00

  • Quantum-chemical analysis of C-H...O and C-H...N interactions in RNA base pairs--H-bond versus anti-H-bond pattern.

    abstract::Geometries and interaction energies of unusual UU and AA base pairs with one standard hydrogen bond (H-bond) and additional C-H...O or C-H...N contacts have been determined by quantum-chemical methods taking into account electron correlation. Whereas the C-H bond length in the UU C-H...O contact increases upon complex...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2001.10506687

    authors: Brandl M,Meyer M,Sühnel J

    更新日期:2001-02-01 00:00:00

  • Molecular modeling study of the norfloxacin-DNA complex.

    abstract::Molecular modeling and molecular dynamics were performed to investigate the interaction of norfloxacin with the DNA oligonucleotide 5'-d(ATACGTAT)(2). Eight quinolone-DNA binding structures were built by molecular modeling on the basis of experimental results. A 100ps molecular dynamics calculation was carried out on ...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2002.10506811

    authors: Lee HM,Kim JK,Kim SK

    更新日期:2002-06-01 00:00:00

  • Novel approach for structural identification of protein family: glyoxalase I.

    abstract::Glyoxalase is one of two enzymes of the glyoxalase detoxification system against methylglyoxal and other aldehydes, the metabolites derived from glycolysis. The glyoxalase system is found almost in all living organisms: bacteria, protozoa, plants, and animals, including humans, and is related to the class of 'life ess...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2017.1367330

    authors: Kargatov AM,Boshkova EA,Chirgadze YN

    更新日期:2018-08-01 00:00:00

  • Selective binding of synthetic polypeptides to DNA of varying composition and sequence: effect of minor groove binding drugs.

    abstract::Repetitive basic polypeptides containing lysine or arginine as every third amino acid were shown to cause DNA condensation at physiological salt concentration connected with selective DNA binding with respect to DNA composition and sequence. This selectivity is very similar to that existing in the case of histone H1 a...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.1996.10508912

    authors: Sponar J,Votavová H

    更新日期:1996-06-01 00:00:00

  • Mid-infrared study of deoxyadenosine at high pressures: evidence of phase transitions.

    abstract::Room temperature mid-infrared experiments between 500 and 1800 cm(-1) have been performed on crystalline deoxyadenosine as a function of pressure up to about 10 GPa. Discontinuities observed near 2 and 4 GPa indicate that two separate phase transitions occur at these pressures. Changes in the spectra suggest that both...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2007.10507147

    authors: Lee SA,Lettress L,Anderson A

    更新日期:2007-06-01 00:00:00

  • Study on the interaction of taiwaniaquinoids with FTO by spectroscopy and molecular modeling.

    abstract::In this work, an attempt has been made to study the interaction of four taiwaniaquinoids with fat mass and obesity-associated protein (FTO) by UV-vis absorption, fluorescence spectroscopy, and molecular docking techniques. The results indicated that taiwaniaquinoids effectively quenched the intrinsic fluorescence of F...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2016.1249957

    authors: Ren T,Zhang L,Wang J,Song C,Wang R,Chang J

    更新日期:2017-11-01 00:00:00

  • The interaction of beta-lactoglobulin with ciprofloxacin and kanamycin; a spectroscopic and molecular modeling approach.

    abstract::A vast research has been conducted to find suitable and safe carriers for vital and pH-sensitive drugs including antibiotics. This article reports the use of easily accessible and abundant purified beta-lactoglobulin (β-LG) protein as the potential carrier of widely used Kanamycin (Kana) and Ciprofloxacin (Cip) antibi...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2016.1203819

    authors: Mehraban MH,Odooli S,Yousefi R,Roghanian R,Motovali-Bashi M,Moosavi-Movahedi AA,Ghasemi Y

    更新日期:2017-07-01 00:00:00

  • Virtual screening, docking, and dynamics of potential new inhibitors of dihydrofolate reductase from Yersinia pestis.

    abstract::In the present work, we propose to design drugs that target the enzyme dihydrofolate redutase (DHFR) as a means of a novel drug therapy against plague. Potential inhibitors of DHFR from Yersinia pestis (YpDHFR) were selected by virtual screening and subjected to docking, molecular dynamics (MD) simulations, and Poisso...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2015.1110832

    authors: Bastos Lda C,de Souza FR,Guimarães AP,Sirouspour M,Cuya Guizado TR,Forgione P,Ramalho TC,França TC

    更新日期:2016-10-01 00:00:00

  • Simulated annealing for alpha-helical protein folding: searches in vicinity of the "molten globule" state.

    abstract::A new model for simulation of protein folding of alpha-helical proteins with known secondary structure is proposed. We are dealing here with the analysis of alpha-helix packings rather than with a detailed atom structure of a whole protein. Starting from a random compact packing of the helices the search is focused on...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.1998.10508232

    authors: Grigoriev IV,Rakhmaninova AB,Mironov AA

    更新日期:1998-08-01 00:00:00

  • In silico site-directed mutagenesis of neutralizing mAb 4C4 and analysis of its interaction with G-H loop of VP1 to explore its therapeutic applications against FMD.

    abstract::Investigating the behaviour of bio-molecules through computational mutagenesis is gaining interest to facilitate the development of new therapeutic solutions for infectious diseases. The antigenetically variant genotypes of foot and mouth disease virus (FMDV) and their subsequent infections are challenging to tackle w...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2018.1494631

    authors: Sahu TK,Pradhan D,Rao AR,Jena L

    更新日期:2019-07-01 00:00:00

  • Polyelectrolyte effects on 9-aminoacridine-DNA binding.

    abstract::The 9-aminoacridine-DNA binding curve is analyzed in two ways: with polyelectrolyte effects neglected and with polyelectrolyte effects included. It is found that the analysis which includes polyelectrolyte effects is consistent with the violation of neighbor exclusion displayed by diacridine complexes as observed by A...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.1991.10507861

    authors: Friedman RA,Shahin M,Zuckerbraun S

    更新日期:1991-04-01 00:00:00

  • Molecular dynamics of anthraquinone DNA intercalators with polyethylene glycol side chains.

    abstract::The interactions of a homologous series of four anthraquinone (AQ) intercalators with increasing lengths of polyethylene glycol (PEG) side chains with DNA have been studied via molecular dynamics (MD) simulations. The geometry, conformation, interactions, and hydration of the complexes were examined. The geometries of...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/073911012010525031

    authors: Beckford SJ,Dixon DW

    更新日期:2012-01-01 00:00:00

  • Deciphering structural stability and binding mechanisms of potential antagonists with smoothened protein.

    abstract::Identification of new potential inhibitors against Hedgehog pathway activator protein Smoothened (SMO) is considered to be of higher importance to improvise the future cancer therapeutics. Different SMO inhibitors/drugs (e.g. Cyclopamine, Vismodegib, Taladegib) used till date are found to be associated with several dr...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2017.1372310

    authors: Sinha N,Chowdhury S,Sarkar RR

    更新日期:2018-08-01 00:00:00

  • Structural and dynamic aspects of non-intercalative (1:1) binding of a thiazole-lexitropsin to the decadeoxyribonucleotide d-[CGCAATTGCG]2: An 1H-NMR and molecular modeling study.

    abstract::The location, orientation and dynamics of a thiazole-containing analogue of distamycin 1 bound to the decadeoxyribonucleotide d-[CGCAATTGCG]2 have been studied by non-exchangable and imino proton NMR resonances of the 1:1 complex. Using NOE difference, COSY and NOESY experiments, lexitropsin (1) was located in the min...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.1991.10507890

    authors: Kumar S,Bathini Y,Joseph T,Pon RT,Lown JW

    更新日期:1991-08-01 00:00:00