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Sai Manohar Chelli, Parth Gupta, Siva Kumar Belliraj
Soft spot analysis helps evaluate the site of the metabolic lability that impacts the bio-availability of the drug. However, given its laborious and time consuming experimentation, we propose a reliable and cheap in silico strategy. In this context, we hypothesized a mechanistic rationale for metabolism of erlotinib by the CYP3A4 enzyme. The comparison of the 3D conformations of the target CYP class of enzymes using MD simulations with GROMACS helped evaluate its impact on the metabolism. The molecular docking studies using Autodock-Vina ascertained the explicit role of the Fe ion present in the Heme moiety in this process...
February 14, 2019: Journal of Molecular Modeling
Junchao Xia, William Flynn, Emilio Gallicchio, Keith Uplinger, Jonathan D Armstrong, Stefano Forli, Arthur J Olson, Ronald M Levy
To perform massive-scale replica exchange molecular dynamics (REMD) simulations for calculating binding free energies of protein-ligand complexes, we implemented the asynchronous replica exchange (AsyncRE) framework of the binding energy distribution analysis method (BEDAM) in implicit solvent on the IBM World Community Grid (WCG) and optimized the simulation parameters to reduce the overhead and improve the prediction power of the WCG AsyncRE simulations. We also performed the first massive-scale binding free energy calculations using the WCG distributed computing gird and 301 ligands from the SAMPL4 challenge for large-scale binding free energy predictions of HIV-1 integrase complexes...
February 13, 2019: Journal of Chemical Information and Modeling
Huma Khan, Varun Jaiswal, Saurabh Kulshreshtha, Azhar Khan
BACKGROUND: Hypertension is the chronic medical condition and it affect billions of people worldwide. Natural medicines are the main alternatives of treatment for a large majority of people suffering from hypertension. Niazicin-A, Niazimin-A, and Niaziminin-B compounds were reported from Moringa oleifera ethanolic leave extract having potential antihypertensive activity. OBJECTIVE: These compounds targeted with Angiotensin-converting enzyme [ACE] which is one of the main regulatory enzymes of the renin-angiotensin system...
February 10, 2019: Recent Patents on Biotechnology
Shazi Shakil
Alzheimer's disease, a neurodegenerative disorder continues to be an area of investigation by the international researchers' fraternity. Despite all the ongoing efforts, the effective set of promising cholinesterase inhibitors available in the market for patients' use is limited. Furthermore, the currently available drugs could provide only a palliative type of treatment instead of providing a complete cure or foolproof prevention. Hence, design/discovery of fresh drug molecules as acetylcholinesterase (AChE) inhibitors still remains an urgent requirement...
February 11, 2019: Journal of Cellular Biochemistry
Reaz Uddin, Noor-Ul-Ain Zahra, Syed Sikander Azam
Tuberculosis (TB) is a major global health challenge. It has been afflicting human for thousands of years and is still severely affecting a huge population. The etiological agent of the disease is Mycobacterium tuberculosis (MTB) that survives in the human host in latent, dormant, and non-replicative state by evading the immune system. It is one of the leading causes of infection related death worldwide. The situation is exacerbated by the massive increase in the resistant strains such as multi-drug resistant TB (MDR-TB) and extensive drug-resistant TB (XDR-TB)...
January 24, 2019: Computational Biology and Chemistry
Thomas L Gonzalez, James M Rae, Justin A Colacino, Rudy J Richardson
Crystal structures exist for human, but not rodent, estrogen receptor-α ligand-binding domain (ERα-LBD). Consequently, rodent studies involving binding of compounds to ERα-LBD are limited in their molecular-level interpretation and extrapolation to humans. Because the sequences of rodent and human ERα-LBDs are > 95% identical, we expected their 3D structures and ligand binding to be highly similar. To test this hypothesis, we used the human ERα-LBD structure (PDB 3UUD) as a template to produce rat and mouse homology models...
May 2019: Computational Toxicology
Piyush Agrawal, Harinder Singh, Hemant Kumar Srivastava, Sandeep Singh, Gaurav Kishore, Gajendra P S Raghava
BACKGROUND: Molecular docking studies on protein-peptide interactions are a challenging and time-consuming task because peptides are generally more flexible than proteins and tend to adopt numerous conformations. There are several benchmarking studies on protein-protein, protein-ligand and nucleic acid-ligand docking interactions. However, a series of docking methods is not rigorously validated for protein-peptide complexes in the literature. Considering the importance and wide application of peptide docking, we describe benchmarking of 6 docking methods on 133 protein-peptide complexes having peptide length between 9 to 15 residues...
February 4, 2019: BMC Bioinformatics
Akanksha Sharma, M Hayatul Islam, Nida Fatima, Tarun K Upadhyay, M Kalim A Khan, Upendra N Dwivedi, Rolee Sharma
Tuberculosis (TB) is a leading cause of mortality amongst infectious diseases. While the anti-TB drugs can cure TB, the non-compliance and rapidly increasing resistance is of serious concern. The study aimed to search novel potent inhibitor(s) against MabA and PKS18 targets of Mycobacterium tuberculosis (M.tb.) by virtual screening of anthraquinones from marine fungi. The target proteins MabA and PKS18 involved in M.tb. mycolic acid biosynthesis were retrieved from RCSB Protein Data Bank. Chemical structures of 100 marine fungal anthraquinones were retrieved from the PubChem database...
February 4, 2019: Molecular Biology Reports
Halima Nebeg, Khedidja Benarous, Talia Serseg, Asma Lazreg, Hafidha Hassani, Mohamed Yousfi
BACKGROUND AND OBJECTIVE: Lipase inhibitors have aroused a great interest because they could help in the therapy of many diseases but, unfortunately, only a few drugs are currently available on the market. Therefore, the aim of this work was to evaluate for the first time the lipase inhibition effect of Thapsia garganica extracts from seeds, leaves and roots. METHODS: Polyphenols and flavonoids contents were determined using spectrophotometric method. Inhibitory activity of ethyl acetate extracts from seeds, leaves and roots of T...
January 28, 2019: Endocrine, Metabolic & Immune Disorders Drug Targets
Vaishali M Patil, Preeti Anand, Monika Bhardwaj, Neeraj Masand
The research work aims to investigate Schiff bases of Cinnamaldehyde as biologically potent analogs. In the past decade CADD has emerged as a rational approach in drug development so with the help molecular docking approach we planned to perform virtual screening of the designed data set of Schiff bases. This will be helpful to put some light on the drug receptor interactions required for anti-inflammatory activity. For carrying out virtual screening of the developed Schiff base data set, AutoDock 4.0 was used...
January 25, 2019: Current Drug Discovery Technologies
Amina Asghar, Muhammad Yousuf, Hifsa Mubeen, Rabia Nazir, Kabiru Haruna, Abdulmujeeb T Onawole, Lubna Rasheed
A mutual prodrug (1) of ibuprofen and sulphanilamide has been synthesized with dual activity and improved toxicity profile. The synthesized compound has been characterized by elemental analysis, FT-IR, 1 HNMR, 13 CNMR and ESI-MS. The molecular geometry of the compound (1) was optimized using density functional theory (DFT/B3LYP) method with the 6-311G(d,p) basis sets in ground state. Geometric parameters (bond lengths, bond angles, torsion angles), vibrational assignments, chemical shifts and thermodynamics of the compound (1) has been calculated theoretically and compared with the experimental data...
January 17, 2019: Bioorganic & Medicinal Chemistry
Pawel Pasznik, Ewelina Rutkowska, Szymon Niewieczerzal, Judyta Cielecka-Piontek, Dorota Latek
The prolonged use of many currently available drugs results in the severe side effect of the disruption of glucose metabolism leading to type 2 diabetes mellitus (T2DM. Gut hormone receptors including glucagon receptor (GCGR) and the incretin hormone receptors: glucagon-like peptide 1 receptor (GLP1R) and gastric inhibitory polypeptide receptor (GIPR) are important drug targets for the treatment of T2DM, as they play roles in the regulation of glucose and insulin levels and of food intake. In this study, we hypothesized that we could compensate for the negative influences of specific drugs on glucose metabolism by the positive incretin effect enhanced by the off-target interactions with incretin GPCR receptors...
2019: PloS One
Diyana Mohd Isa, Sek Peng Chin, Wei Lim Chong, Sharifuddin M Zain, Noorsaadah Abd Rahman, Vannajan Sanghiran Lee
In this study, we investigate the binding interactions of two synthetic antiviral peptides (DET2 and DET4) on type II dengue virus (DENV2) envelope protein domain III. These two antiviral peptides are designed based on the domain III of the DENV2 envelope protein, which has shown significant inhibition activity in previous studies and can be potentially modified further to be active against all dengue strains. Molecular docking was performed using AutoDock Vina and the best-ranked peptide-domain III complex was further explored using molecular dynamics simulations...
January 24, 2019: Journal of Biological Physics
Amit Jayaswal, Hirdyesh Mishra, Ankita Mishra, Kavita Shah
HIV is one of the most lethal viral diseases in the human population. Patients often suffer from drug resistance, which hampers HIV therapy. Eleven different structural analogues of saquinavir (SQV), designed using ChemSketch™ and named S1 through S11, were compared with SQV with respect to their pharmacodynamic and pharmacokinetic properties. Pharmacokinetic predictions were carried out using AutoDock, and molecular docking between macromolecule HIV protease (PDB ID: 3IXO) and analogues S1 - S11 as ligands was performed...
January 24, 2019: Archives of Virology
Franklyn Nonso Iheagwam, Olubanke Olujoke Ogunlana, Oluseyi Ebenezer Ogunlana, Itunuoluwa Isewon, Jelili Oyelade
Tyrosine kinase (TK), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMP) are important cancer therapeutic target proteins. Based on reported anti-cancer and cytotoxic activities of Caesalpinia bonduc , this study isolated phytochemicals from young twigs and leaves of C bonduc and identified the interaction between them and cancer target proteins (TK, VEGF, and MMP) in silico. AutoDock Vina, iGEMDOCK, and analysis of pharmacokinetic and pharmacodynamic properties of the isolated bioactives as therapeutic molecules were performed...
2019: Bioinformatics and Biology Insights
Xiaodong Sun, Kang Liu, Yingxiang Du, Jie Liu, Xiaofei Ma
Recently, chiral ionic liquids (CILs) have received increasing interest in chiral separation by capillary electrophoresis. Nevertheless, the lack of deep perception of the specific mechanism about CILs in CE for enantioseparation still perplexes a legion of researchers, despite the strenuous efforts. In this paper, a lactobionic acid based ionic liquid, tetramethylammonium-lactobionate (TMA-LA) was applied for the first time in CE to establish dual selector system with clindamycin phosphate (CP) for enantiomeric separation...
January 21, 2019: Electrophoresis
Aarti Dalal, Parvin Kumar, Radhika Khanna, Dinesh Kumar, Deepika Paliwal, Ramesh C Kamboj
A series of 1-{2-(prop-2-ynyloxy)aryl}-3-hydroxy-3-(4'-trifluoromethyl-phenyl)prop-2-en-1-ones obtained by photo-irradiation of 2-{2-(prop-2-ynyloxy)benzoyl}-3-(4-trifluoromethyl-phenyl)oxiranes (that were characterized by spectral studies: FT-IR, 1H NMR, 13C NMR and Mass analysis) was screened for the anti-malarial activity by evaluating against chloroquine-sensitive P. falciparum (CD7). The molecular docking studies using AutoDock Vina were also performed to further ascertain the efficacy of these compounds with PDB:4ORM...
January 15, 2019: Infectious Disorders Drug Targets
Arthur O Zalevsky, Alexander S Zlobin, Vasilina R Gedzun, Roman V Reshetnikov, Maxim L Lovat, Anton V Malyshev, Igor I Doronin, Gennady A Babkin, Andrey V Golovin
Peptides are promising drug candidates due to high specificity and standout safety. Identification of bioactive peptides de novo using molecular docking is a widely used approach. However, current scoring functions are poorly optimized for peptide ligands. In this work, we present a novel algorithm PeptoGrid that rescores poses predicted by AutoDock Vina according to frequency information of ligand atoms with particular properties appearing at different positions in the target protein's ligand binding site...
January 13, 2019: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Sahil Jain, Manoj Baranwal
Computational approach has shown remarkable progress in epitope mapping, paving the way to finding vaccine candidates against different viruses. In the current study, prediction algorithms and molecular docking were applied to select peptides containing multiple Ebola glycoprotein epitopes showing interaction with different HLA molecules. Six peptides containing overlapping multiple HLA I (CD8+ ) and II (CD4+ ) restricted T cell epitopes were generated via consensus approach applying six different prediction tools...
January 9, 2019: Journal of Theoretical Biology
Subrata Laskar, Omar Espino, Debasish Bandyopadhyay
BACKGROUND: Abrus precatorius Linn. (Kunch in Bengali) is widely spread in tropical and sub-tropical regions. It is a typical plant species which is well-known simultaneously as folk medicine and for its toxicity. OBJECTIVE: Phytoceutical investigation of the white variety seeds of Abrus precatorius Linn. METHOD: Traditional extraction, separation, isolation, and purification processes were followed. The structure was elucidated by various spectral analyses and the solid-state structure of this indole-alkaloid has been determined by X-ray crystallographic analysis...
January 10, 2019: Current Cancer Drug Targets
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