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
  • Strong nucleosomes of A. thaliana concentrate in centromere regions.

    abstract::Earlier identified strongest nucleosome DNA sequences of A. thaliana, those with visible 10-11 base sequence periodicity, are mapped along chromosomes. Resulting positional distributions reveal distinct maxima, one per chromosome, located in the centromere regions. Sequence-directed nucleosome mapping demonstrates tha...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2013.860624

    authors: Salih B,Trifonov EN

    更新日期:2015-01-01 00:00:00

  • Statistical mechanical approach for predicting the transition to non-B DNA structures in supercoiled DNA.

    abstract::Supercoiling causes global twist of DNA structure and the supercoiled state has wide influence on conformational transition. A statistical mechanical approach was made for prediction of the transition probability to non-B DNA structures under torsional stress. A conditional partition function was defined as the sum ov...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.1993.10507997

    authors: Katsura S,Makishima F,Nishimura H

    更新日期:1993-02-01 00:00:00

  • Prediction of potential inhibitors against SARS-CoV-2 endoribonuclease: RNA immunity sensing.

    abstract::The World Health Organization has classified the COVID-19 outbreak a pandemic which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and declared it a global health emergency. Repurposing drugs with minimum side effects are one approach to quickly respond in attempt to prevent the spread of CO...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2020.1863265

    authors: Al-Rashedi NAM,Munahi MG,Ah ALObaidi L

    更新日期:2020-12-27 00:00:00

  • In silico 3D structure modeling and inhibitor binding studies of human male germ cell-associated kinase.

    abstract::Human male germ cell-associated kinase (hMAK) is an androgen-inducible gene in prostate epithelial cells, and it acts as a coactivator of androgen receptor signaling in prostate cancer. The 3D structure of the hMAK kinase was modeled based on the crystal structure of CDK2 kinase using comparative modeling methods, and...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2014.968622

    authors: Tanneeru K,Balla AR,Guruprasad L

    更新日期:2015-01-01 00:00:00

  • The binding process of BmKTX and BmKTX-D33H toward to Kv1.3 channel: a molecular dynamics simulation study.

    abstract::The potassium channel Kv1.3 is an important pharmacological target and the Kaliotoxin-type toxins (α-KTX-3 family) are its specific blockers. Here, we study the binding process of two kinds of Kaliotoxin-type toxins:BmKTX and its mutant (BmKTX-D33H) toward to Kv1.3 channel using MD simulation and umbrella sampling sim...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2020.1760135

    authors: Zheng Q,Na R,Yang L,Yu H,Zhao X,Huang X

    更新日期:2020-05-06 00:00:00

  • Effect of compatible and noncompatible osmolytes on the enzymatic activity and thermal stability of bovine liver catalase.

    abstract::Catalase is an important antioxidant enzyme that catalyzes the disproportionation of H2O2 into harmless water and molecular oxygen. Due to various applications of the enzyme in different sectors of industry as well as medicine, the enhancement of stability of the enzyme is important. Effect of various classes of compa...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2012.742460

    authors: Sepasi Tehrani H,Moosavi-Movahedi AA,Ghourchian H,Ahmad F,Kiany A,Atri MS,Ariaeenejad Sh,Kavousi K,Saboury AA

    更新日期:2013-12-01 00:00:00

  • New insight into the molecular mechanism of the trehalose effect on urate oxidase stability.

    abstract::Urate oxidase (EC 1.7.3.3) is a key enzyme in the purine metabolism which is applied in the treatment of gout and also, as a diagnostic reagent for uric acid detection. In the current study, the trehalose (TRE) effects as an additive on the structural stability and function of uricase were investigated. For recombinan...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2020.1828167

    authors: Taherimehr Z,Zaboli M,Torkzadeh-Mahani M

    更新日期:2020-10-01 00:00:00

  • Analysis of Delta-Notch interaction by molecular modeling and molecular dynamic simulation studies.

    abstract::Notch is a single-pass transmembrane receptor protein. Delta (member of the DSL protein family), a Notch ligand, is also single-pass transmembrane protein that can interact with Notch to form the Delta-Notch complex. It has been demonstrated that of the 36 Epidermal Growth Factor (EGF) repeats of Notch, 11th and 12th ...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2012.674184

    authors: Majumder R,Roy S,Thakur AR

    更新日期:2012-01-01 00:00:00

  • Characterization of the structural conformation adopted by (TTAGGG)n telomeric DNA repeats of different length in closed circular DNA.

    abstract::Telomeric DNA sequences are known to adopt unusual DNA structures upon protonation when contained into negatively supercoiled DNA. In this paper, the structural properties of (T2AG3)n telomeric sequences of different length is analyzed in detail. Transition to the protonated form is observed at very low pH for (T2AG3)...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:

    authors: Huertas D,Lipps H,Azorín F

    更新日期:1994-08-01 00:00:00

  • 1,2,3-Triazole substituted phthalocyanine metal complexes as potential inhibitors for anticholinesterase and antidiabetic enzymes with molecular docking studies.

    abstract::In recent years, acetylcholinesterase (AChE) and α-glycosidase (α-gly) inhibition have emerged as a promising and important approach for pharmacological intervention in many diseases such as glaucoma, epilepsy, obesity, cancer, and Alzheimer's. In this manner, the preparation and enzyme inhibition activities of periph...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2020.1857842

    authors: Koçyiğit ÜM,Taslimi P,Tüzün B,Yakan H,Muğlu H,Güzel E

    更新日期:2020-12-09 00:00:00

  • A conformational analysis of the (+) anti BPDE adduct to the guanine amino group of dCpdG.

    abstract::The (+) anti isomer of benz[a]pyrene diol epoxide (BPDE), 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenz [a] pyrene has been identified as the probable tumorigenic lesion in mammalian systems. It forms a predominant adduct with DNA at N2 of guanine. In order to elucidate its conformation in ...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.1983.10507492

    authors: Hingerty B,Broyde S

    更新日期:1983-12-01 00:00:00

  • Glycation, oxidation and glycoxidation of IgG: a biophysical, biochemical, immunological and hematological study.

    abstract::Glycation and oxidation induce structural alterations in the proteins in an interdependent manner with consequent pathological implications. The published literature presents wide range of modifications in conformational characteristics of proteins by glycation and oxidation; however, there is little data that could e...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2017.1365770

    authors: Islam S,Moinuddin,Mir AR,Raghav A,Habib S,Alam K,Ali A

    更新日期:2018-08-01 00:00:00

  • An in-silico analysis of ivermectin interaction with potential SARS-CoV-2 targets and host nuclear importin α.

    abstract::Ivermectin (IVM) is a broad-spectrum antiparasitic agent, having inhibitory potential against wide range of viral infections. It has also been found to hamper SARS-CoV-2 replication in vitro, and its precise mechanism of action against SARS-CoV-2 is yet to be understood. IVM is known to interact with host importin (IM...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2020.1841028

    authors: Azam F,Taban IM,Eid EEM,Iqbal M,Alam O,Khan S,Mahmood D,Anwar MJ,Khalilullah H,Khan MU

    更新日期:2020-11-02 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

  • Studies on adaptability of binding residues and flap region of TMC-114 resistance HIV-1 protease mutants.

    abstract::Drug resistant mutations have severely restricted the success of HIV therapy. These mutations frequently involve the aspartic protease encoded by the virus. Knowledge of the molecular mechanisms underlying the conformational changes of HIV-1 protease mutants may be useful in developing more effective and longer lastin...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2011.10507379

    authors: Purohit R,Rajendran V,Sethumadhavan R

    更新日期:2011-08-01 00:00:00

  • Density functional theory based probe of the affinity interaction of saccharide ligands with extra-cellular sialic acid residues.

    abstract::Changes in glycosylation pattern leads to malignant transformations among the cells. In combination with upregulated actions of sialyltransferases, it ultimately leads to differential expression of sialic acid (SA) at cell surface. Given its negative charge and localization to extracellular domain, SA has been exploit...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2018.1461690

    authors: Patel A,Tiwari S,Jha PK

    更新日期:2019-04-01 00:00:00

  • HMG box proteins interact with multiple tandemly repeated (GCC)n (GGC)m DNA sequences.

    abstract::A number of tandemly repeated DNA sequences have the ability to form hairpin structures by forming non-standard base pairs. When (GCC)15 and (GGC)15 strands are annealed together, the expected duplex is the only product. However, when (GCC)15 is annealed with (GCC)10, depending on the relative concentrations, up to fi...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.1996.10508113

    authors: Zhao Y,Cheng W,Gibb CL,Gupta G,Kallenbach NR

    更新日期:1996-10-01 00:00:00

  • Structure-based discovery of phenyl-diketo acids derivatives as Mycobacterium tuberculosis malate synthase inhibitors.

    abstract::Mycobacterium tuberculosis remains one of the most successful bacterial pathogens worldwide. The development of drug-resistant strains and the ability of the bacteria to persist in a latent form in the host are major problems for tuberculosis (TB) control. Glyoxylate shunt is a metabolic bypass of the Krebs cycle and ...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2020.1758787

    authors: Shukla R,Shukla H,Tripathi T

    更新日期:2020-04-30 00:00:00

  • Refined homology model of cytochrome bcc complex B subunit for virtual screening of potential anti-tuberculosis agents.

    abstract::Cytochrome bcc complex is important for ATP synthesis and cellular activity, as a crucial step in the terminal reduction of oxygen in aerobic electron transport chains. The b subunit of cytochrome bcc complex (QcrB) has been reported as a promising anti-tuberculosis target, with many novel anti-tuberculosis scaffolds ...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2019.1688196

    authors: Pan Z,Wang Y,Gu X,Wang J,Cheng M

    更新日期:2020-10-01 00:00:00

  • Nonionic but water soluble, [Glycine-Pd-Alanine] and [Glycine-Pd-Valine] complexes. Their synthesis, characterization, antitumor activities and rich DNA/HSA interaction studies.

    abstract::Two novel, neutral and water soluble Pd(II) complexes of formula [Pd(Gly)(Ala)] (1) and [Pd(Gly)(Val)] (2) (Gly, Ala, and Val are anionic forms of glycine, alanine, and valine amino acids, respectively) have been synthesized and characterized by FT-IR, UV-Vis, 1H-NMR, elemental analysis, and molar conductivity measure...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2018.1520647

    authors: Mansouri-Torshizi H,Zareian-Jahromi S,Abdi K,Saeidifar M

    更新日期:2019-08-01 00:00:00

  • Transmembrane helix 6 observed at the interface of β2AR homodimers in blind docking studies.

    abstract::Peptide- and protein-protein dockings were carried out on β2-adrenergic receptor (β2AR) to confirm the presence of transmembrane helix 6 (TM6) at the interface region between two β2AR monomers, thereby its possible role in dimerization as suggested in numerous experimental and computational studies. Initially, a porti...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2014.962094

    authors: Koroglu A,Akten ED

    更新日期:2015-01-01 00:00:00

  • Unique hole-trapping property of the human telomere sequence.

    abstract::The hypothetical protection of genes from oxidative damage provided by the G-rich telomeric overhangs located at the end of chromosomes, which consist, in humans, of single strands of TTAGGG sequence repeats, is investigated here. First principle Moller-Plesset perturbation theory calculations reveal that the TTAGGG h...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2011.10507405

    authors: Cauët E

    更新日期:2011-12-01 00:00:00

  • Nucleosome positioning by sequence, state of the art and apparent finale.

    abstract::All major suggestions about the nucleosome positioning sequence pattern(s) are overviewed. Two basic binary periodical patterns are well established: in purine/pyrimidine alphabet - YRRRRRYYYYYR and in strong/weak alphabet -SWWWWWSSSSSW. Their merger in four-letter alphabet sequence coincides with first ever complete ...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/073911010010524944

    authors: Trifonov EN

    更新日期:2010-06-01 00:00:00

  • Exploring the nature of the H-bonds between the human class II MHC protein, HLA-DR1 (DRB*0101) and the influenza virus hemagglutinin peptide, HA306-318, using the quantum theory of atoms in molecules.

    abstract::The nature of the H-bonds between the human protein HLA-DR1 (DRB*0101) and the hemagglutinin peptide HA306-318 has been studied using the Quantum Theory of Atoms in Molecules for the first time. We have found four H-bond groups: one conventional CO··HN bond group and three nonconventional CO··HC, π··HC involving aroma...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2017.1418432

    authors: Aray Y,Aguilera-García R,Izquierdo DR

    更新日期:2019-01-01 00:00:00

  • Amygdalin as multi-target anticancer drug against targets of cell division cycle: double docking and molecular dynamics simulation.

    abstract::Cell-division protein kinases (CDKs) are gorgeous examples of targets for the helpful treatment of cancer by using multi-target inhibitors. Specifically, targeting cell-division protein kinase1/cyclin B (CDK1/Cyclin B), cell-division protein kinase 2/cyclin A (CDK2/Cyclin A) and cell-division protein kinase 4/cyclin D...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2020.1742792

    authors: Al-Khafaji K,Taskin Tok T

    更新日期:2020-03-24 00:00:00

  • Investigating the binding mechanism of novel 6-aminonicotinate-based antagonists with P2Y12 by 3D-QSAR, docking and molecular dynamics simulations.

    abstract::P2Y12 receptor is an attractive target for the anti-platelet therapies, treating various thrombotic diseases. In this work, a total of 107 6-aminonicotinate-based compounds as potent P2Y12 antagonists were studies by a molecular modeling study combining three-dimensional quantitative structure-activity relationship (3...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2016.1237381

    authors: Zhou S,Fang D,Tan S,Lin W,Wu W,Zheng K

    更新日期:2017-10-01 00:00:00

  • Exploring the binding interactions of janus green blue with serum albumins from spectroscopic and calorimetric studies aided by in silico calculations.

    abstract::Binding interactions of the phenazinium dye Janus green blue (JGB) with human and bovine serum albumins (BSA - and BSA) have been explored for the first time from multi-spectroscopic and calorimetric measurements aided by in silico calculations. The formation of ground state complexes between JGB and the respective se...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2020.1870156

    authors: Saha S,Bhattacharjee S,Chowdhury J

    更新日期:2021-01-07 00:00:00

  • Cooperative hydrogen bonds and mobility of the non-aromatic ring as selectivity determinants for human acetylcholinesterase to similar anti-Alzheimer's galantaminics: a computational study.

    abstract::Galantamine (Gnt) is a natural alkaloid inhibitor of acetylcholinesterase and is presently one of the most used drugs in the treatment against Alzheimer's disease during both the initial and intermediate stages. Among several natural Gnt derivatives, sanguinine (Sng) and lycoramine (Lyc) attract attention because of t...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2018.1470036

    authors: Rocha REO,Lima LHF

    更新日期:2019-04-01 00:00:00

  • Molecular docking and molecular dynamics simulations of a mutant Acinetobacter haemolyticus alkaline-stable lipase against tributyrin.

    abstract::We previously reported on a mutant lipase KV1 (Mut-LipKV1) from Acinetobacter haemolyticus which optimal pH was raised from 8.0 to 11.0 after triple substitutions of surface aspartic acid (Asp) with lysine (Lys). Herein, this study further examined the Mut-LipKV1 by molecular docking, molecular dynamics (MD) simulatio...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2020.1743364

    authors: Anuar NFSK,Wahab RA,Huyop F,Amran SI,Hamid AAA,Halim KBA,Hood MHM

    更新日期:2020-03-23 00:00:00

  • Surface modified PAMAM dendrimers with gallic acid inhibit, cell proliferation, cell migration and inflammatory response to augment apoptotic cell death in human colon carcinoma cells.

    abstract::To overcome the obstacle of anti-cancer therapy significant attention has been drawn for improving drug delivery system. Since recent past, different approaches were applied using synthetic or natural derivatives for improving efficacy of anti-cancer drugs in cancer therapeutics. Gallic acid (GA) is a natural polyphen...

    journal_title:Journal of biomolecular structure & dynamics

    pub_type: 杂志文章

    doi:10.1080/07391102.2020.1802344

    authors: Priyadarshi K,Shirsath K,Waghela NB,Sharma A,Kumar A,Pathak C

    更新日期:2020-08-05 00:00:00