排序方式: 共有9条查询结果,搜索用时 15 毫秒
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Parasuraman Aiya Subramani Venkata Ramireddy Narala R Dinakaran Michael Dakshayani Lomada Madhava C Reddy 《Bioinformation》2015,11(5):248-253
Protein prenylation is a posttranslational modification that is indispensable for translocation of membrane GTPases like Ras, Rho,
Ras etc. Proteins of Ras family undergo farnesylation by FTase while Rho family goes through geranylgeranylation by GGTase1.
There is only an infinitesimal difference in signal recognition between FTase and GGTase1. FTase inhibitors mostly end up
selecting the cells with mutated Ras proteins that have acquired affinity towards GGTase1 in cancer microcosms. Therefore, it is of
interest to identify GGTase1 and FTase dual inhibitors using the docking tool AutoDock Vina. Docking data show that curcumin
(from turmeric) has higher binding affinity to GGTase1 than that of established peptidomimetic GGTase1 inhibitors (GGTI) such as
GGTI-297, GGTI-298, CHEMBL525185. Curcumin also interacts with FTase with binding energy comparable to co-crystalized
compound 2-[3-(3-ethyl-1-methyl-2-oxo-azepan-3-yl)-phenoxy]-4-[1-amino-1-(1-methyl-1h-imidizol-5-yl)-ethyl]-benzonitrile (BNE).
The docked complex was further simulated for 10 ns using molecular dynamics simulation for stability. Thus, the molecular basis
for curcumin binding to GGTase1 and FTase is reported. 相似文献
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Alexandra M. Harsa Teodora E. Harsa 《Journal of enzyme inhibition and medicinal chemistry》2016,31(3):508-515
Forty anthraquinone derivatives have been downloaded from PubChem database and investigated in a quantitative structure-activity relationships (QSAR) study. The models describing log P and LD50 of this set were built up on the hypermolecule scheme that mimics the investigated receptor space; the models were validated by the leave-one-out procedure, in the external test set and in a new version of prediction by using similarity clusters. Molecular docking approach using Lamarckian Genetic Algorithm was made on this class of anthraquinones with respect to 3Q3B receptor. The best scored molecules in the docking assay were used as leaders in the similarity clustering procedure. It is demonstrated that the LD50 data of this set of anthraquinones are related to the binding energies of anthraquinone ligands to the 3Q3B receptor. 相似文献
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《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):569-575
In some human cancer cases, the activity of p53 is inhibited by over-expressed Mdm2. The Mdm2 acts as an ubiquitin ligase, resulting in p53 ubiquitination and subsequent p53 proteasomal degradation. The disruption of the Mdm2-p53 interaction using small-molecule inhibitors is recognized as a promising strategy for anti-cancer drug design. Mushrooms are an important source of powerful compounds with anti-tumour properties. In this study, the first virtual screening of low molecular weight compounds present in mushroom is presented as potential Mdm2 inhibitors. A re-docking and cross-docking method was used to validate the virtual screening protocol. The steroids: ganoderic acids X (Ki?=?16nM), Y (Ki?=?22nM) and F (Ki?=?69nM); 5,6-epoxy-24(R)-methylcholesta-7,22-dien-3β-ol (Ki?=?74nM) and polyporenic acid C (Ki?=?59nM) stand out as the top ranked potential inhibitors of Mdm2. The docking pose of the most promising compounds were carefully analysed and the information provided shows several interesting starting points for further development of Mdm2 inhibitors. 相似文献
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Nuclear Factor κ B is implicated in tumor progression and chronic inflammatory diseases and is regulated by IκB kinase β (IKKβ). The crystal structure of IKKβ has been recently solved for Xenopus laevis. Homology models of human IKKβ have been developed prior to and after the crystal structure was solved. Here, we compare four models of human IKKβ and evaluate their performance in both broad and focused library docking studies. 相似文献
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随着大量与细菌耐药相关的基因的发现和其表达蛋白结构的成功测定,从已有的化合物中通过计算机模拟方法筛选对耐药蛋白靶点有作用的候选化合物,成为了药物发现的一个标准途径。虚拟筛选在耐药基因抑制剂的发现中可以提高效率、降低实验成本。本文介绍了Autodock Vina和Discovery Studio在基于分子对接法的虚拟筛选中的使用,并对比分析其对β-内酰胺酶活性位点的筛选结果。希望通过这种比较促进虚拟筛选在药物设计领域中的应用,提高耐药基因抑制剂的发现速度。 相似文献
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Multiple drug resistance (MDR) in bacteria is a global health challenge that needs urgent attention.
The 2011 outbreak caused by Escherichia coli O104:H4 in Europe has exposed the inability of present antibiotic
arsenal to tackle the problem of antimicrobial infections. It has further posed a tremendous burden on entire
pharmaceutical industry to find novel drugs and/or drug targets. Polyphosphate kinase (PPK) in bacteria plays
a crucial role in helping latter to adapt to stringent conditions of low nutritional availability thus making
it a good target for antibacterials. In spite of this critical role, to best of our knowledge no in-silico work
has been carried out to develop PPK as an antibiotic target. In the present study, virtual screening of PPK
was carried out against all the 3D compounds with pharmacological action present in PubChem database. Our
screening results were further refined by interaction maps to eliminate the false positive data respectively.
From our results, compound number 5281927 (PubChem ID) has been found to have significant affinity towards
affinity towards PPK active ATP-binding site indicating its therapeutic relevance. 相似文献
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Noreen K. Nkosana Daniel J. Czyzyk Zarek S. Siegel Joy M. Cote Erika A. Taylor 《Bioorganic & medicinal chemistry letters》2018,28(4):594-600
Gram-negative bacteria comprise the majority of microbes that cause infections that are resistant to pre-existing antibiotics. The complex cell wall architecture contributes to their ability to form biofilms, which are often implicated in hospital-acquired infections. Biofilms promote antibiotic resistance by enabling the bacteria to survive hostile environments such as UV radiation, pH shifts, and antibiotics. The outer membrane of Gram-negative bacteria contains lipopolysaccharide (LPS), which plays a role in adhesion to surfaces and formation of biofilms. The main focus of this work was the synthesis of a library of glycolipids designed to be simplified analogues of the Lipid A, the membrane embedded portion component of LPS, to be tested as substrates or inhibitors of Heptosyltransferase I (HepI or WaaC, a glycosyltransferase enzyme involved in the biosynthesis of LPS). Fourteen analogues were synthesized successfully and characterized. While these compounds were designed to function as nucleophilic substrates of HepI, they all demonstrated mild inhibition of HepI. Kinetic characterization of inhibition mechanism identified that the compounds exhibited uncompetitive and mixed inhibition of HepI. Since both uncompetitive and mixed inhibition result in the formation of an Enzyme-Substrate-inhibitor complex, molecular docking studies (using AutoDock Vina) were performed, to identify potential allosteric binding site for these compounds. The inhibitors were shown to bind to a pocket formed after undergoing a conformational change from an open to a closed active site state. Inhibition of HepI via an allosteric site suggest that disruption of protein dynamics might be a viable mechanism for the inhibition of HepI and potentially other enzymes of the GT-B structural class. 相似文献
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《Peptides》2017
Niemann-Pick C1 like-1 (NPC1L1) mediates cholesterol absorption at the apical membrane of enterocytes through a yet unknown mechanism. Bean, pea, and lentil proteins are naturally hydrolyzed during digestion to produce peptides. The potential for pulse peptides to have high binding affinities for NPC1L1 has not been determined. In this study , in silico binding affinities and interactions were determined between the N-terminal domain of NPC1L1 and 14 pulse peptides (5≥ amino acids) derived through pepsin-pancreatin digestion. Peptides were docked in triplicate to the N-terminal domain using docking program AutoDock Vina, and results were compared to those of ezetimibe, a prescribed NPC1L1 inhibitor. Three black bean peptides (−7.2 to −7.0 kcal/mol) and the cowpea bean dipeptide Lys-Asp (−7.0 kcal/mol) had higher binding affinities than ezetimibe (−6.6 kcal/mol) for the N-terminal domain of NPC1L1. Lentil and pea peptides studied did not have high binding affinities. The common bean peptide Tyr-Ala-Ala-Ala-Thr (−7.2 kcal/mol), which can be produced from black or navy bean proteins, had the highest binding affinity. Ezetimibe and peptides with high binding affinities for the N-terminal domain are expected to interact at different locations of the N-terminal domain. All high affinity black bean peptides are expected to have van der Waals interactions with SER130, PHE136, and LEU236 and a conventional hydrogen bond with GLU238 of NPC1L1. Due to their high affinity for the N-terminal domain of NPC1L1, black and cowpea bean peptides produced in the digestive track have the potential to disrupt interactions between NPC1L1 and membrane proteins that lead to cholesterol absorption. 相似文献
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