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Protein-protein docking

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https://www.readbyqxmd.com/read/29058231/computational-design-of-new-protein-kinase-d-1-pkd1-inhibitors-homology-based-active-site-prediction-energy-optimized-pharmacophore-docking-and-database-screening
#1
Nalini, Navriti Chadha, Malkeet Singh Bahia, Maninder Kaur, Renu Bahadur, Om Silakari
Protein kinase D 1 (PKD1) overexpression has a well-validated role in cancer progression and its inhibitors have defined a protective role-play of PKD1 for various cancers such as prostate, pancreatic and noninvasive breast cancers, and more. Therefore, the current research was aimed at designing new PKD1 inhibitors combining different ligand- and structure-based computational drug designing methodologies. Initially, the three-dimensional structure of PKD1's active site was computationally modeled, corrected using molecular dynamic simulations and validated for docking experiments...
October 23, 2017: Molecular Diversity
https://www.readbyqxmd.com/read/29058101/dock8-deficiency-presenting-as-an-ipex-like-disorder
#2
Fayhan J Alroqi, Louis-Marie Charbonnier, Sevgi Keles, Fatima Ghandour, Pierre Mouawad, Rami Sabouneh, Reem Mohammed, Abduarahman Almutairi, Janet Chou, Michel J Massaad, Raif S Geha, Zeina Baz, Talal A Chatila
PURPOSE: The dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive-combined immunodeficiency whose clinical spectra include recurrent infections, autoimmunity, malignancies, elevated serum IgE, eczema, and food allergies. Here, we report on patients with loss of function DOCK8 mutations with profound immune dysregulation suggestive of an immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX)-like disorder. METHODS: Immunophenotyping of lymphocyte subpopulations and analysis of DOCK8 protein expression were evaluated by flow cytometry...
October 23, 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/29057709/structural-model-of-the-full-length-ser-thr-protein-kinase-stkp-from-s-pneumoniae-and-its-recognition-of-peptidoglycan-fragments
#3
Benedetta Righino, Frédéric Galisson, Davide Pirolli, Serena Vitale, Stéphane Réty, Patrice Gouet, Maria Cristina De Rosa
The unique eukaryotic-likeSer/Thrprotein kinases of S. pneumoniae, StkP, plays a primary role inthe cell division process. Itis composed of an intracellular kinase domain, a transmembrane helix and four extracellular PASTA subunits. PASTA domains were shown to interact with cell wall fragments but the key questions related to the molecular mechanism governing ligand recognition remain unclear. To address this issue, the full-length structural model of StkP was generated by combining small-angle X-ray scattering data with the results of computer simulations...
October 23, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29055857/coumarinyl-pyranopyrimidines-as-new-neuropeptide-s-receptor-antagonists-design-synthesis-homology-and-molecular-docking
#4
Rasha Z Batran, Dina H Dawood, Samia A El-Seginy, Timothy J Maher, Kuljeet S Gugnani, Alejandro N Rondon-Ortiz
In this work, we described the design, synthesis and characterization of a new class of NPSR antagonists bearing the tetracyclic coumarinyl pyranopyrimidine scaffold incorporated with different acyclic and/or heterocyclic moieties. These compounds are highlighted in this study as never being used as NPSR antagonists before which provides a model for the discovery of new bioactive inhibitors that may hold potential for drug development towards anxiety, food, and addiction disorders. Synthetic and medicinal chemistry studies led to the identification of four potent antagonists, compounds 7d, 10, 12 and 13, which were able to significantly inhibit the stimulatory effect of NPS through counteracting the increased intracellular Ca(2+) accumulation...
October 12, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29055806/new-generation-of-docking-programs-supercomputer-validation-of-force-fields-and-quantum-chemical-methods-for-docking
#5
Alexey V Sulimov, Danil C Kutov, Ekaterina V Katkova, Ivan S Ilin, Vladimir B Sulimov
Discovery of new inhibitors of the protein associated with a given disease is the initial and most important stage of the whole process of the rational development of new pharmaceutical substances. New inhibitors block the active site of the target protein and the disease is cured. Computer-aided molecular modeling can considerably increase effectiveness of new inhibitors development. Reliable predictions of the target protein inhibition by a small molecule, ligand, is defined by the accuracy of docking programs...
October 12, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29054801/why-do-antifreeze-proteins-require-a-solenoid
#6
M Banach, L Konieczny, I Roterman
Proteins whose presence prevents water from freezing in living organisms at temperatures below 0 °C are referred to as antifreeze proteins. This group includes molecules of varying size (from 30 to over 300 aa) and variable secondary/supersecondary conformation. Some of these proteins also contain peculiar structural motifs called solenoids. We have applied the fuzzy oil drop model in the analysis of four categories of antifreeze proteins: 1 - very small proteins, i.e. helical peptides (below 40 aa); 2 - small globular proteins (40-100 aa); 3 - large globular proteins (>100 aa) and 4 - proteins containing solenoids...
October 17, 2017: Biochimie
https://www.readbyqxmd.com/read/29054521/computational-simulations-and-experimental-validation-of-structure-physicochemical-properties-of-pristine-and-functionalized-graphene-implications-for-adverse-effects-on-p53-mediated-dna-damage-response
#7
Faiza Basheer, Anu R Melge, Abhilash Sasidharan, Shantikumar V Nair, K Manzoor, C Gopi Mohan
Recent reports indicated DNA damaging potential of few-layer graphene in human cell systems. Here, we used computational technique to understand the interaction of both pristine (pG) or carboxyl functionalized graphene (fG) of different sizes (1, 6, and 10nm) with an important DNA repair protein p53. The molecular docking study revealed strong interaction between pG and DNA binding domains (DBD) of p53 with binding free energies (BE) varying from -12.0 (1nm) to -34 (6nm)kcal/mol, while fG showed relatively less interaction with BE varying from -6...
October 17, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29053956/assembly-of-the-whip-trim14-ppp6c-mitochondrial-complex-promotes-rig-i-mediated-antiviral-signaling
#8
Peng Tan, Lian He, Jun Cui, Chen Qian, Xin Cao, Meng Lin, Qingyuan Zhu, Yinyin Li, Changsheng Xing, Xiao Yu, Helen Y Wang, Rong-Fu Wang
Mitochondrial antiviral signaling platform protein (MAVS) acts as a central hub for RIG-I receptor proximal signal propagation. However, key components in the assembly of the MAVS mitochondrial platform that promote RIG-I mitochondrial localization and optimal activation are still largely undefined. Employing pooled RNAi and yeast two-hybrid screenings, we report that the mitochondrial adaptor protein tripartite motif (TRIM)14 provides a docking platform for the assembly of the mitochondrial signaling complex required for maximal activation of RIG-I-mediated signaling, consisting of WHIP and protein phosphatase PPP6C...
October 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29052925/structural-insights-into-natural-compounds-as-inhibitors-of-fasciola-gigantica-thioredoxin-glutathione-reductase
#9
Rohit Shukla, Harish Shukla, Parismita Kalita, Timir Tripathi
Fascioliasis is caused by the helminth parasites of genus Fasciola. Thioredoxin glutathione reductase (TGR) is an important enzyme in parasitic helminths and plays an indispensable role in its redox biology. In the present study, we conducted a structure-based virtual screening of natural compounds against the Fasciola gigantica TGR (FgTGR). The compounds were docked against FgTGR in four sequential docking modes. The screened ligands were further assessed for Lipinski and ADMET prediction so as to evaluate drug proficiency and likeness property...
October 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29052792/prediction-of-binding-poses-to-fxr-using-multi-targeted-docking-combined-with-molecular-dynamics-and-enhanced-sampling
#10
Soumendranath Bhakat, Emil Åberg, Pär Söderhjelm
Advanced molecular docking methods often aim at capturing the flexibility of the protein upon binding to the ligand. In this study, we investigate whether instead a simple rigid docking method can be applied, if combined with multiple target structures to model the backbone flexibility and molecular dynamics simulations to model the sidechain and ligand flexibility. The methods are tested for the binding of 35 ligands to FXR as part of the first stage of the Drug Design Data Resource (D3R) Grand Challenge 2 blind challenge...
October 20, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/29051098/impact-of-tyrosine-nitration-at-positions-tyr307-and-tyr335-on-structural-dynamics-of-lipoprotein-associated-phospholipase-a2-a-therapeutically-important-cardiovascular-biomarker-for-atherosclerosis
#11
Arun Bahadur Gurung, Atanu Bhattacharjee
Protein tyrosine nitration (PTN) is a post translational event which results in the generation of 3-Nitrotyrosine (3-NT). High levels of 3-NT were reported in several human diseases such as Parkinson's disease, Alzheimer's disease, amylotrophic lateral sclerosis and coronary artery disease. It was reported that PTN at positions 307 and 335 of Lipoprotein-associated phospholipase A2 (Lp-PLA2) curtails its enzymatic activity but the mechanism of inhibition at the structure level is still incomprehensible. The present study is an in silico endeavor to understand nitrative stress induced structural changes in Lp-PLA2...
October 16, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29048609/two-novel-atypical-pkc-inhibitors-acpd-and-dnda-effectively-mitigate-cell-proliferation-and-epithelial-to-mesenchymal-transition-of-metastatic-melanoma-while-inducing-apoptosis
#12
Wishrawana S Ratnayake, André H Apostolatos, David A Ostrov, Mildred Acevedo-Duncan
Atypical protein kinase Cs (aPKC) are involved in cell cycle progression, tumorigenesis, cell survival and migration in many cancers. We believe that aPKCs play an important role in cell motility of melanoma by regulating cell signaling pathways and inducing epithelial to mesenchymal transition (EMT). We have investigated the effects of two novel aPKC inhibitors; 2-acetyl-1,3-cyclopentanedione (ACPD) and 3,4-diaminonaphthalene-2,7-disulfonic acid (DNDA) on cell proliferation, apoptosis, migration and invasion of two malignant melanoma cell lines compared to normal melanocytes...
September 22, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29047404/structural-and-functional-characterization-of-the-divergent-entamoeba-src-using-src-inhibitor-1
#13
Luilli López-Contreras, Verónica Ivonne Hernández-Ramírez, Mayra Herrera-Martínez, Sarita Montaño, Luis Alejandro Constantino-Jonapa, Bibiana Chávez-Munguía, Patricia Talamás-Rohana
BACKGROUND: The abundant number of kinases that Entamoeba histolytica possesses allows us to assume that the regulation of cellular functions by phosphorylation-dephosphorylation processes is very important. However, the kinases responsible for the phosphorylation in Entamoeba spp. vary in the structure of their domains and, therefore, could be responsible for the unusual biological characteristics of this parasite. In higher eukaryotes, Src kinases share conserved structural domains and are very important in the regulation of the actin cytoskeleton...
October 18, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/29046143/influence-of-length-and-amino-acid-composition-on-dimer-formation-of-immunoglobulin-based-chimera
#14
Patidar Manoj, Yadav Naveen, Sarat Kumar Dalai
BACKGROUND: The dimeric immunoglobulin (Ig) chimeras used for drug targeting and delivery are preferred biologics over their monomeric forms. Designing these Ig chimeras involves critical selection of a suitable Ig base that ensures dimer formation. In the present study, we systematically analyzed several factors that influence the formation of dimeric chimera. We designed and predicted 608 cytokine-Ig chimeras where we tested the contributions of (1) different domains of Ig constant heavy chain, (2) length of partner proteins, (3) amino acid (AA) composition and (4) position of cysteine in the formation of homodimer...
October 18, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29045929/deciphering-the-complexation-process-of-a-fluoroquinolone-antibiotic-levofloxacin-with-bovine-serum-albumin-in-the-presence-of-additives
#15
Amandeep Kaur, Imran Ahmd Khan, Parampaul Kaur Banipal, Tarlok Singh Banipal
The current work aims to explore the thermodynamic and conformational aspects for the binding of fluoroquinolone antibacterial drug, levofloxacin (LFC), with bovine serum albumin (BSA) using calorimetric, spectroscopic (UV-visible, fluorescence, circular dichroism, and (1)H NMR), dynamic light scattering (DLS) and computational methods (molecular docking). The binding of LFC with BSA at two sequential sites with higher affinity (~10(3)M(-1)) at the first site has been explored by calorimetry whereas the binding at a single site with affinity of the order of ~10(4)M(-1) has been observed from fluorescence spectroscopy...
October 9, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/29045746/identification-of-natural-products-as-inhibitors-of-human-organic-anion-transporters-oat1-and-oat3-and-their-protective-effect-on-mercury-induced-toxicity
#16
Xue Wang, Lifeng Han, Gentao Li, Wei Peng, Xiumei Gao, Curtis D Klaassen, Guanwei Fan, Youcai Zhang
Mercury accumulates in kidneys and produces acute kidney injury. Semen cassiae (SC), a widely consumed tea and herbal medicine in Eastern Asia, has been reported to have protective effects on kidneys. In this study, SC extract was shown to almost abolish the histological alterations induced by mercuric chloride (HgCl2) in rat kidneys. A total of 22 compounds were isolated from SC, and 1,7,8-methoxyl-2-hydroxyl-3-methyl-anthraquinone was detected in SC for the first time. Among the 8 compounds identified in the blood of rats after SC treatment, 6 were strong inhibitors of human organic anion transporter 1 and 3 (OAT1 and OAT3)...
October 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29045039/design-of-potent-b-raf-v600e-inhibitors-by-mcss-strategy
#17
Ze-Feng Wang, Peng-Fei Wang, Jun-Ting Ma, Ying-Zi Chai, Hui-Min Hu, Wen-Long Gao, Zhong-Chang Wang, Bao-Zhong Wang, Hai-Liang Zhu
B-Raf kinase is a vital intermedium in the mitogen-activated protein kinase (MAPK) signaling pathway, which transforms extracellular signals into cellular mechanisms. Mutations in this kinase, for instance, the most common V600E mutation, can lead to the ERK signaling pathologically activated and hence cause severe diseases like somatic tumors. So far, the development of B-Raf inhibitors has made remarkable progress. However, the resistance and relapse of approved Raf drugs have been widely reported, and the optimization for old drugs and the discovery for new inhibitors still remain a significant task...
October 17, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29042617/expression-and-function-of-abcg4-in-the-mouse-blood-brain-barrier-role-in-restricting-the-brain-entry-of-amyloid-%C3%AE-peptide
#18
Agnès Dodacki, Matthew Wortman, Bruno Saubaméa, Stéphanie Chasseigneaux, Sophie Nicolic, Nathalie Prince, Murielle Lochus, Anne-Laure Raveu, Xavier Declèves, Jean-Michel Scherrmann, Shailendra B Patel, Fanchon Bourasset
ABCG4 is an ATP-binding cassette transmembrane protein which has been shown, in vitro, to participate in the cellular efflux of desmosterol and amyloid-β peptide (Aβ). ABCG4 is highly expressed in the brain, but its localization and function at the blood-brain barrier (BBB) level remain unknown. We demonstrate by qRT-PCR and confocal imaging that mouse Abcg4 is expressed in the brain capillary endothelial cells. Modelling studies of the Abcg4 dimer suggested that desmosterol showed thermodynamically favorable binding at the putative sterol-binding site, and this was greater than for cholesterol...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29041840/identification-of-novel-scaffolds-to-inhibit-human-mitotic-kinesin-eg5-targeting-the-second-allosteric-binding-site-using-in-silico-methods
#19
Himesh Makala, Venkatasubramanian Ulaganathan
Human mitotic kinesins are potential anticancer drug targets because of their essential role in mitotic cell division. The kinesin Eg5 (Kinesin-5, kif11) has gained much attention in this regard and has many inhibitors in different phases of clinical trials. All drug candidates considered for Eg5 so far binds to the binding site (Site 1) formed by the loop L5, helices α2 and α3 and are uncompetitive to ATP/ADP. Recently, it has been reported that Eg5 also has a second binding site (Site 2) formed by helices α4 and α6...
October 17, 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/29040952/design-synthesis-kinetic-mechanism-and-molecular-docking-studies-of-novel-1-pentanoyl-3-arylthioureas-as-inhibitors-of-mushroom-tyrosinase-and-free-radical-scavengers
#20
Fayaz Ali Larik, Aamer Saeed, Pervaiz Ali Channar, Urooj Muqadar, Qamar Abbas, Mubashir Hassan, Sung-Yum Seo, Michael Bolte
A series of novel 1-pentanoyl-3-arylthioureas was designed as new mushroom tyrosinase inhibitors and free radical scavengers. The title compounds were obtained in excellent yield and characterized by FTIR, (1)H NMR, (13)C NMR and X-ray crystallography in case of compound (4a). The inhibitory effects on mushroom tyrosinase and DPPH were evaluated and it was observed that 1-Pentanoyl-3-(4-methoxyphenyl) thiourea (4f) showed tyrosinase inhibitory activity (IC50 1.568 ± 0.01 mM) comparable to Kojic acid (IC50 16...
September 29, 2017: European Journal of Medicinal Chemistry
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