当前位置： SCI文献检索 > Current Computer-Aided Drug Design期刊下所有文献 > Integrating Multiple Receptor Conformation Docking and Multi Dimensional QSAR for Enhancing Accuracy of Binding Affinity Prediction.

Integrating Multiple Receptor Conformation Docking and Multi Dimensional QSAR for Enhancing Accuracy of Binding Affinity Prediction.

Abstract：

BACKGROUND:The accuracy of molecular conformation for Quantitative Structure Activity Relationship (QSAR) studies is an important criteria, and the most favourable bioactive conformer selection is a tough task. Correct ligand alignment as input for 3D-QSAR is an important step that is prone to human biases. Multiple-dimensional QSAR (mQSAR) approach provides a promising alternative to classic 3D-QSAR for drug discovery purposes. OBJECTIVE:Obtaining ligand conformations from multiple receptor conformation docking (MRCD) will reduce the margin of error by incorporating the receptor based alignment of ligand conformations. To validate this assumption we performed 6D QSAR studies on reported HIV-1 protease inhibitors using Quasar 6.0. MATERIALS & METHOD:The ensemble of conformation was obtained by MRCD of ligands in thirteen crystal structures of HIV-1 protease. 6D QSAR model was built using 65 cyclic urea molecules reported as HIV-1 protease inhibitors. Predictive ability of the model was validated using 35 cyclic urea molecules as test set. External predictive ability of the model was evaluated using a set of 24 HIV-1 protease inhibitors having varied structural scaffold. RESULT:6D QSAR model obtained showed a reliable cross-validated r2(q2) of 0.899, r2(classic) of 0.908 and yielded a predictive r2 (p2) of 0.527. The ratio of q2/r2 was 0.991 and p2/q2 was 0.586 for external test set. CONCLUSION:The QSAR results invariably suggest that our approach is suitable for the identification of molecules having HIV-1 protease inhibitory potency. The underlying philosophy combines flexible docking for the identification of the binding modes and 6D QSAR for their quantification.

journal_name

Curr Comput Aided Drug Des

journal_title

Current computer-aided drug design

authors

Radhika V,Jaraf HA,Kanth SS,Vijjulatha M

doi

10.2174/1573409913666170119115841

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

127-142

issue

2

eissn

1573-4099

issn

1875-6697

pii

CAD-EPUB-81174

journal_volume

13

pub_type

杂志文章

相关文献

Current Computer-Aided Drug Design文献大全
  • Integrated ligand based pharmacophore model derived from diverse FAAH covalent ligand classes.

    abstract：:3D pharmacophore modeling is an important computational methodology for ligand-enzyme binding interactions in drug discovery. More specifically, a consensus pharmacophore model derived from diverse ligands is a key determinant upon which the prediction power of computational models is based for designing novel ligands...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/157340912803519615

    authors： Shen L,Huang H,Makriyannis A,Fisher LS

    更新日期：2012-12-01 00:00:00

  • QSAR Models for the Reactivation of Sarin Inhibited AChE by Quaternary Pyridinium Oximes Based on Monte Carlo Method.

    abstract：:For three random splits, one-variable models of oximes reactivation of sarin inhibited acetylcholinesterase (logarithm of the AChE reactivation percentage by oximes with concentration of 0.001 M) have been calculated with CORAL software. The total number of considered oximes was 42. Simplified molecular input line ent...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：

    authors： Veselinović AM,Veselinović JB,Toropov AA,Toropova AP,Nikolić GM

    更新日期：2014-11-26 00:00:00

  • Pharmacophore and Docking Guided Virtual Screening Study for Discovery of Type I Inhibitors of VEGFR-2 Kinase.

    abstract：BACKGROUND:Kinase domain of VEGFR-2 displays conformational flexibility which leads to existence of two kinds of inhibitors viz. type I and type II inhibitors. They exhibit different binding modes and this necessitates the development of separate pharmacophore models for them. METHODS:The virtual screening study for d...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/1386207319666161214112536

    authors： Bhojwani HR,Joshi UJ

    更新日期：2017-01-01 00:00:00

  • Quantitative structure-activity relationship model, molecular docking simulation and computational design of some novel compounds against DNA gyrase receptor.

    abstract：INTRODUCTION:Mycobacterium tuberculosis has instigated a serious challenge toward the effective treatment of tuberculosis. The reoccurrence of the resistant strains of the disease to accessible drugs/medications has mandate for the development of more effective anti-tubercular agents with efficient activities. Time exp...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/1573409916666200625142447

    authors： Adeniji SE

    更新日期：2020-06-25 00:00:00

  • Shannon's, mutual, conditional and joint entropy information indices: generalization of global indices defined from local vertex invariants.

    abstract：:A new mathematical approach is proposed in the definition of molecular descriptors (MDs) based on the application of information theory concepts. This approach stems from a new matrix representation of a molecular graph (G) which is derived from the generalization of an incidence matrix whose row entries correspond to...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/1573409911309020003

    authors： Barigye SJ,Marrero-Ponce Y,Santiago OM,López YM,Pérez-Giménez F,Torrens F

    更新日期：2013-06-01 00:00:00

  • Structural Insights into the Molecular Design of ROS1 Inhibitor for the Treatment of Non-Small Cell Lung Cancer (NSCLC).

    abstract：BACKGROUND:The Non-Small Cell Lung Cancer (NSCLC) alone is responsible for the sovereignty of demises worldwide related to the other cancers.ROS1 is a receptor tyrosine kinase (RTK), eminently recognized as the stereotyped oncogenic driver. These RTKs trigger an array of physiological regulations via cellular signal tr...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/1573409916666200504105249

    authors： Adhikary R,Khandelwal R,Hussain T,Nayarisseri A,Singh SK

    更新日期：2020-05-03 00:00:00

  • Novel Thiosemicarbazide Hybrids with Amino Acids and Peptides Against Hepatocellular Carcinoma: A Molecular Designing Approach Towards Multikinase Inhibitor.

    abstract：:Hepatocellular Carcinoma is the most common primary malignant tumor of the liver. Development of multidrug resistance is the main obstacle to the success of anticancer drugs. In this study, designing and docking study of thiosemicarbazide hybrids with amino acids or peptides against hepatocellular carcinoma was perfor...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/1573409911666151103114300

    authors： Chacko S,Samanta S

    更新日期：2015-01-01 00:00:00

  • Mixed ligand-metal Complexes of 2-(butan-2-ylidene) hydrazinecarbothioamide- Synthesis, Characterization, Computer Aided Drug Character Evaluation and in vitro Biological Activity Assessment.

    abstract：BACKGROUND:Mixed ligand-metal complexes are efficient chelating agents because of flexible donor ability. Mixed ligand complexes containing hetero atoms sulphur, nitrogen and oxygen have been probed for their biological significance. OBJECTIVE:Nine mixed ligand-metal complexes of 2-(butan-2-ylidene) hydrazinecarbothio...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/1573409915666190926122103

    authors： Khan T,Ahmad R,Azad I,Raza S,Joshi S,Khan AR

    更新日期：2019-09-26 00:00:00

  • Systematic generation of chemical structures for rational drug design based on QSAR models.

    abstract：:The first step in the process of drug development is to determine those lead compounds that demonstrate significant biological activity with regard to a target protein. Because this process is often costly and time consuming, there is a need to develop efficient methodologies for the generation of lead compounds for p...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章,评审

    doi：10.2174/157340911793743556

    authors： Funatsu K,Miyao T,Arakawa M

    更新日期：2011-03-01 00:00:00

  • In Silico Design of Fusion Toxin DT389GCSF and a Comparative Study.

    abstract：BACKGROUND:Chemotherapy and radiotherapy have negative effects on normal tissues and they are very expensive and lengthy treatments. These disadvantages have recently attracted researchers to the new methods that specifically affect cancerous tissues and have lower damage to normal tissues. One of these methods is the ...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/1573409914666181012151242

    authors： Siahmazgi MG,Khalili MAN,Ahmadpour F,Khodadadi S,Zeinoddini M

    更新日期：2020-01-01 00:00:00

  • Screening of Potential Lead Molecule as Novel MurE Inhibitor: Virtual Screening, Molecular Dynamics and In Vitro Studies.

    abstract：BACKGROUND:The prevalence of multi-drug resistance S. aureus is one of the most challenging tasks for the treatment of nosocomial infections. Proteins and enzymes of peptidoglycan biosynthesis pathway are one among the well-studied targets, but many of the enzymes are unexplored as targets. MurE is one such enzyme feat...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/1573409912666161010142943

    authors： Zaveri K,Kiranmayi P

    更新日期：2017-01-01 00:00:00

  • Structure Activity Relationship Studies of Gymnemic Acid Analogues for Antidiabetic Activity Targeting PPARγ.

    abstract：:Diabetes accounts for high mortality rate worldwide affecting million of lives annually. Global prevalence of diabetes and its rising frequency makes it a key area of research in drug discovery programs. The research article describes the development of quantitative structure activity relationship model against PPARγ,...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/1573409911666150610093611

    authors： Tiwari P,Sharma P,Khan F,Sangwan NS,Mishra BN,Sangwan RS

    更新日期：2015-01-01 00:00:00

  • 3D-QSAR Selectivity Analysis of 1-Adamantyl-3-Heteroaryl Urea Analogs as Potent Inhibitors of Mycobacterium tuberculosis.

    abstract：:A 3D-QSAR selectivity analysis of 53 adamantyl heteroaryl urea derivatives active against M. tuberculosis is reported. These analogs inhibit Mycobacterial Membrane Protein Large 3 (MmpL3), a proposed transporter for cell wall mycolic acids. However, these analogs also exhibit affinity towards human soluble epoxide hyd...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/1573409911666150803154114

    authors： Wadhwa P,Bagchi S,Sharma A

    更新日期：2015-01-01 00:00:00

  • Computerassisted models for Blood Brain Barrier permeation of 1, 5-Benzodiazepines.

    abstract：AIM:To generate and validate predictive models for blood brain permeation (BBB) of CNS molecules using QSPR approach. BACKGROUND:Prediction of molecules crossing BBB remain a challenge in drug delivery. Predictive models are designed for evaluation of set of preclinical drugs which may serve as alternatives for determ...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/1573409916666200131114018

    authors： Dhavale RP,Choudhari PB,Bhatia MS

    更新日期：2020-01-30 00:00:00

  • Experimental and computational studies on the inhibition of acetylcholinesterase by curcumin and some of its derivatives.

    abstract：:Recent studies have demonstrated several biological activities of curcumin with therapeutic potential against Alzheimer's disease, among them the inhibition of the enzyme acetylcholinesterase (AChE). Aiming at identifying the chemical features relevant for this activity, the inhibition of curcumin and a set of 7 deriv...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/15734099113099990007

    authors： Tello-Franco V,Lozada-García MC,Soriano-García M

    更新日期：2013-06-01 00:00:00

  • A Drug Decision Support System for Developing a Successful Drug Candidate Using Machine Learning Techniques.

    abstract：BACKGROUND:Virtual screening of candidate drug molecules using machine learning techniques plays a key role in pharmaceutical industry to design and discovery of new drugs. Computational classification methods can determine drug types according to the disease groups and distinguish approved drugs from withdrawn ones. ...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/1573409915666190716143601

    authors： Onay A,Onay M

    更新日期：2020-01-01 00:00:00

  • Importance of Kier-Hall topological indices in the QSAR of anticancer drug design.

    abstract：:An important area of theoretical drug design research is quantitative structure activity relationship (QSAR) using structural invariants. The impetus for this research trend comes from various directions. Researchers in chemical documentation have searched for a set of invariants which will be more convenient than the...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章,评审

    doi：10.2174/157340912800492384

    authors： Nandi S,Bagchi MC

    更新日期：2012-06-01 00:00:00

  • Prospects of Wedelolactone as a Chemotherapeutic Agent in Gynecological Cancers; Clue From its In Vitro and In Silico Investigation.

    abstract：BACKGROUND:Identification and development of new drug candidates to be used singly or in combination therapy is critical in anticancer research. In recent years, accumulating evidence encouraged us to investigate the anti-proliferative effects of a small and emerging phytochemical Wedelolactone (WDL) in estrogen-depend...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/1573409915666191015113134

    authors： Sarwar S,Amed T,Qazi NG,Yu JQ,Huq F

    更新日期：2020-01-01 00:00:00

  • QSTR studies regarding the ECOSAR toxicity of benzene-carboxylic acid' esters to fathead minnow fish (Pimephales promelas).

    abstract：:The present work employs 152 benzene-carboxylic acid' esters having computed the toxicity within the range [2.251, 10.222] for fathead minnow fish (Pimephales promelas). Calibration set includes many pairs having very similar chemical structure, size, shape and hydrophilicity, but very different value of ECOSAR toxici...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/1573409910666140410094056

    authors： Tarko L,Putz MV,Ionascu C,Putz AM

    更新日期：2014-01-01 00:00:00

  • Modeling the interactions between alpha(1)-adrenergic receptors and their antagonists.

    abstract：:As crucial members of the G-protein coupled receptor (GPCR) superfamily, alpha (1)-adrenergic receptors (alpha(1)-ARs) are recognized to intervene the actions of endogenous catecholamines such as norepinephrine and epinephrine. So far three distinct alpha(1)-AR subtypes, alpha(1A), alpha(1B) and alpha(1D), have been c...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章,评审

    doi：10.2174/157340910791760082

    authors： Du L,Li M

    更新日期：2010-09-01 00:00:00

  • Computational models for 5αR inhibitors for treatment of prostate cancer: review of previous works and screening of natural inhibitors of 5αR2.

    abstract：:Taking into consideration the high importance of the drug target 5-α-reductase (5αR) in prostate cancer in this work we are going first to review previous works and discuss works related to the computer aided drug design of 5αR inhibitors. We report new results in the in silico screening of natural 5αR inhibitors. Tra...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章,评审

    doi：10.2174/157340911798260368

    authors： Jayadeepa RM,Sharma S

    更新日期：2011-12-01 00:00:00

  • QSAR of Chalcones Utilizing Theoretical Molecular Descriptors.

    abstract：:The paper is an attempt for QSAR modeling based on topological, electrostatic, quantum chemical, constitutional, geometrical and physicochemical indices computed from the structures of 59 set of synthesized chalcone derivatives tested for the cell cycle inhibition of mitotic G2/M phase using multiple linear regression...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/1573409911666150702101559

    authors： Nandi S,Bagchi MC

    更新日期：2015-01-01 00:00:00

  • Multi-target QSAR and docking study of steroids binding to corticosteroid-binding globulin and sex hormone-binding globulin.

    abstract：:The QSAR and docking studies were performed on fifty seven steroids with binding affinities for corticosteroid-binding globulin (CBG) and eighty four steroids with binding affinities for sex hormone-binding globulin (SHBG). Since the steroidal compounds have binding affinity for both CBG and SHBG, multi-target QSAR ap...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/157340912803519642

    authors： Nikolic K,Filipic S,Agbaba D

    更新日期：2012-12-01 00:00:00

  • Salient Aspects of PBP2A-inhibition; A QSAR Study.

    abstract：BACKGROUND:Inhibition of penicillin binding protein 2A (PBP2A) represents a sound drug design strategy in combatting Methicillin resistant Staphylococcus aureus (MRSA). Considering the urgent need for effective antimicrobials in combatting MRSA infections, we have developed a statistically robust ensemble of molecular ...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/1573409914666180516114314

    authors： Ogunleye AJ,Eniafe GO,Inyang OK,Adewumi B,Omotuyi OI

    更新日期：2018-01-01 00:00:00

  • Comparison of Performance of Docking, LIE, Metadynamics and QSAR in Predicting Binding Affinity of Benzenesulfonamides.

    abstract：:The design of inhibitors specific for one relevant carbonic anhydrase isozyme is the major challenge in the new therapeutic agents development. Comparative computational chemical structure and biological activity relationship studies on a series of carbonic anhydrase II inhibitors, benzenesulfonamide derivatives, bear...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/1573409911666150916092624

    authors： Raškevičius V,Kairys V

    更新日期：2015-01-01 00:00:00

  • An Integrated Multi-QSAR Modeling Approach for Designing Knoevenagel- Type Indoles with Enhancing Cytotoxic Profiles.

    abstract：BACKGROUND:Unconventional Knoevenagel-type indoles have been the topic of interest of many synthetic chemists because of its promising efficacy in different diseases including cancer. OBJECTIVE:To explore the structural requirements of Knoevenagel-type cytotoxic indoles for higher efficacy. METHODS:Multi-QSAR modelin...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/1573409913666170309150014

    authors： Amin SA,Adhikari N,Jha T,Gayen S

    更新日期：2017-11-10 00:00:00

  • Pharmacophore Modeling, Docking and Molecular Dynamics Studies on Caspase-3 Activators Binding at β-Tubulin Site.

    abstract：:Induction of apoptosis by the activation of caspase 3 makes it a promising target for designing anticancer drugs hence an investigation for the essential structural features mandatory for caspase 3 activation has been carried out using a dataset comprising of caspase 3 activator candidate drug Azixa in phase II clinic...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/1573409911666150701103342

    authors： Bhunia SS,Singh S,Saxena S,Saxena AK

    更新日期：2015-01-01 00:00:00

  • In Silico Appraisal, Synthesis, Antibacterial Screening and DNA Cleavage for 1,2,5-thiadiazole Derivative.

    abstract：BACKGROUND:Thiadiazole not only acts as "hydrogen binding domain" and "two-electron donor system" but also as constrained pharmacophore. METHODS:The maleate salt of 2-((2-hydroxy-3-((4-morpholino-1, 2,5-thiadiazol-3-yl) oxy) propyl) amino)- 2-methylpropan-1-ol (TML-Hydroxy)(4) has been synthesized. This methodology in...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/1573409915666190206142756

    authors： Mali SN,Sawant S,Chaudhari HK,Mandewale MC

    更新日期：2019-01-01 00:00:00

  • Why so few drug targets: a mathematical explanation?

    abstract：:The apparently paradoxical lack of correlation between the huge increase in the discovery of new potential drug targets made possible by the post-genomic sciences and new drugs development has stimulated many different interpretations. Here we illustrate the general principle of redundancy of biological pathways on ha...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章

    doi：10.2174/157340911796504297

    authors： Tun K,Menghini M,D'Andrea L,Dhar P,Tanaka H,Giuliani A

    更新日期：2011-09-01 00:00:00

  • On the contribution of molecular topology to drug design and discovery.

    abstract：:The role of molecular topology (MT) in the design and selection of new drugs is discussed. After an overview of the different in silico molecular design current technologies, the QSAR analysis is dealt in detail with particular emphasis in the use of topological indices as molecular descriptors. The results of the app...

    journal_title：Current computer-aided drug design

    pub_type： 杂志文章,评审

    doi：10.2174/1573409911006040252

    authors： Gálvez J,García-Doménech R

    更新日期：2010-12-01 00:00:00