185 research outputs found
SwissDock, a protein-small molecule docking web service based on EADock DSS
Most life science processes involve, at the atomic scale, recognition between two molecules. The prediction of such interactions at the molecular level, by so-called docking software, is a non-trivial task. Docking programs have a wide range of applications ranging from protein engineering to drug design. This article presents SwissDock, a web server dedicated to the docking of small molecules on target proteins. It is based on the EADock DSS engine, combined with setup scripts for curating common problems and for preparing both the target protein and the ligand input files. An efficient Ajax/HTML interface was designed and implemented so that scientists can easily submit dockings and retrieve the predicted complexes. For automated docking tasks, a programmatic SOAP interface has been set up and template programs can be downloaded in Perl, Python and PHP. The web site also provides an access to a database of manually curated complexes, based on the Ligand Protein Database. A wiki and a forum are available to the community to promote interactions between users. The SwissDock web site is available online at http://www.swissdock.ch. We believe it constitutes a step toward generalizing the use of docking tools beyond the traditional molecular modeling community
SwissDock, a protein-small molecule docking web service based on EADock DSS
Most life science processes involve, at the atomic scale, recognition between two molecules. The prediction of such interactions at the molecular level, by so-called docking software, is a non-trivial task. Docking programs have a wide range of applications ranging from protein engineering to drug design. This article presents SwissDock, a web server dedicated to the docking of small molecules on target proteins. It is based on the EADock DSS engine, combined with setup scripts for curating common problems and for preparing both the target protein and the ligand input files. An efficient Ajax/HTML interface was designed and implemented so that scientists can easily submit dockings and retrieve the predicted complexes. For automated docking tasks, a programmatic SOAP interface has been set up and template programs can be downloaded in Perl, Python and PHP. The web site also provides an access to a database of manually curated complexes, based on the Ligand Protein Database. A wiki and a forum are available to the community to promote interactions between users. The SwissDock web site is available online at http://www.swissdock.ch. We believe it constitutes a step toward generalizing the use of docking tools beyond the traditional molecular modeling communit
Application of the SwissDrugDesign Online Resources in Virtual Screening.
SwissDrugDesign is an important initiative led by the Molecular Modeling Group of the SIB Swiss Institute of Bioinformatics. This project provides a collection of freely available online tools for computer-aided drug design. Some of these web-based methods, i.e., SwissSimilarity and SwissTargetPrediction, were especially developed to perform virtual screening, while others such as SwissADME, SwissDock, SwissParam and SwissBioisostere can find applications in related activities. The present review aims at providing a short description of these methods together with examples of their application in virtual screening, where SwissDrugDesign tools successfully supported the discovery of bioactive small molecules
Deciphering molecular mechanism of amyloid inhibition through docking studies between amyloid beta peptide and selected small molecules
The misfolding and aggregation of proteins into amyloids has been linked to a large group of variety amyloid -related diseases. This group consists of variety human diseases such as Alzheimers disease, Parkinson’s disease, Hungtington’s disease, atherosclerosis etc. Aggregation of proteins, such as aâ in Alzheimer’s disease, appears to lead to the formation of toxic assemblies. These assemblies can be very small in size like oligomers(consisting of very few proteins) and can reach a maximum of thousands of proteins which leads to fibril formation. It has been found out that inhibiting the aggregation of these proteins could slow down the process of formation of these neurodegerative diseases. But still there is truancy of a possible therapy that could effectively prevent the formation of amyloid fibrils. Thus in present study we try to understand the mechanism by which the small compounds which we have selected inhibits the target protein or the amyloid beta peptide. Here we understand the type of interaction and whether the compounds binds near the amyloidogenic region. We have also tried to understand the binding between two amyloid protein. Here we have choosen an amyloidogenic protein beta amyloid (1-42), pdbid-1IYT, that is processed from the amyloid precursor protein(APP). While best known as the component of amyloid plaques in association with Alzheimer’s disease, as A-beta is the main component of certain deposits found in the brain of patients with Alzheimer’s disease. The small compounds selected here are mostly cholesterol reducing agents such as statins, wine related compounds, green tea related components, polyphenols, phenothiazines. These compounds are found to inhibit amyloid fibrillogenesis in vivo. So here we adduce a mechanism by which these small compounds inhibit the aggregation of amyloid beta(1-42)peptide
Anthranilic Acid Derivatives as Novel Antibiotics against MRSA and other Gram Positive Microorganisms: Combating Antibiotic Resistance
Implementation of antibiotics to treat bacterial infections began during World War II. Since then, a number of antibiotic resistance microorganisms have emerged, one of these being Methicillin Resistant Staphylococcus aureus (MRSA). This resistance can be accredited to multiple factors, but the greatest contributors are the similarity in the chemical composition of the commonly prescribed antibiotics used to treat MRSA and the improper use and disposal of these agents. MRSA is the most frequent health acquired infection in the United States and to combat this growing problem, we have developed a novel class of antibiotics derived from anthranilic acids that show antibacterial activity against MRSA. Our derivatives record a minimum inhibitory concentration (MIC) ranging from 2-64 μg/ml, however when in the presence of human serum protein (HSP) this value increases, decreasing their effectiveness. We have identified a component of HSP, albumin, that causes the increase in MIC, and have determined that intermolecular hydrogen bonding is the cause of this increase. Using this information we are currently synthesizing new derivatives with a low binding affinity for albumin, or when bound do not lose antibacterial activity
PROSPECTIVE BIOLOGICAL ACTIVE COMPOUNDS AMONG 7-SUBSTITUTED OF 3-BENZYL-8-PROPYLXANTHINES FOR TREATMENT OF METABOLIC SYNDROME PATHOLOGIES
Aim – the search for biologically active compounds with diuretic and hypoglycemic action among 7-substituted of 3-benzyl-8-propylxanthines, which can be used for the treatment of pathologies of “metabolic syndrome”.
Materials and methods. 30 new chemical compounds among derivatives of 7-substituted of 3-benzyl-8-propylxanthines by PASS prediction filter were chosen for diuretic and hypoglycemic activity researches. Diuretic, hypoglycemic activity and for the most active compounds – the acute toxicity were studied in vivo. The molecular docking, which is based on EADock DSS mechanism of the modulation displayed the interaction between some of functional groups inside discovered xanthine ligands and known receptors and enzymes presented in Ligand-protein Database of Swiss Institute of Bioinformatics.
Results. It has been shown that synthesized compounds displayed strong diuretic and medium hypoglycemic activities. The molecular docking modulation (SwissDock) of interaction of xanthine derivatives hits with proposed receptors and enzymes revealed prospective of using 7-substituted of 3-benzyl-8-propylxanthines as potential drugs for treatment of metabolic syndrome pathologies.
Conclusion. The diuretic activity of the new 23 compounds of 7-substituted of 3-benzyl-8-propylxanthines and hypoglycemic activity of the new 7 derivatives of 7-substituted of 3-benzyl-8-propylxanthines was studied. Results of performed investigation illustrate that 7-substituted of 3-benzyl-8-propylxanthines demonstrate biological activity comparable to standard drugs. We also proposed probable molecular targets for the most active compounds by molecular docking method. It was shown that derivatives of 7-substituted of 3-benzyl-8-propylxanthines can be used for metabolic syndrome disorders prevention
PROSPECTIVE BIOLOGICAL ACTIVE COMPOUNDS AMONG 7-SUBSTITUTED OF 3-BENZYL-8-PROPYLXANTHINES FOR TREATMENT OF METABOLIC SYNDROME PATHOLOGIES
Aim – the search for biologically active compounds with diuretic and hypoglycemic action among 7-substituted of 3-benzyl-8-propylxanthines, which can be used for the treatment of pathologies of “metabolic syndrome”.
Materials and methods. 30 new chemical compounds among derivatives of 7-substituted of 3-benzyl-8-propylxanthines by PASS prediction filter were chosen for diuretic and hypoglycemic activity researches. Diuretic, hypoglycemic activity and for the most active compounds – the acute toxicity were studied in vivo. The molecular docking, which is based on EADock DSS mechanism of the modulation displayed the interaction between some of functional groups inside discovered xanthine ligands and known receptors and enzymes presented in Ligand-protein Database of Swiss Institute of Bioinformatics.
Results. It has been shown that synthesized compounds displayed strong diuretic and medium hypoglycemic activities. The molecular docking modulation (SwissDock) of interaction of xanthine derivatives hits with proposed receptors and enzymes revealed prospective of using 7-substituted of 3-benzyl-8-propylxanthines as potential drugs for treatment of metabolic syndrome pathologies.
Conclusion. The diuretic activity of the new 23 compounds of 7-substituted of 3-benzyl-8-propylxanthines and hypoglycemic activity of the new 7 derivatives of 7-substituted of 3-benzyl-8-propylxanthines was studied. Results of performed investigation illustrate that 7-substituted of 3-benzyl-8-propylxanthines demonstrate biological activity comparable to standard drugs. We also proposed probable molecular targets for the most active compounds by molecular docking method. It was shown that derivatives of 7-substituted of 3-benzyl-8-propylxanthines can be used for metabolic syndrome disorders prevention
New N,N-dimethylcarbamate inhibitors of acetylcholinesterase: design synthesis and biological evaluation
A series of N,N-dimethylcarbamates containing a N,N-dibenzylamino moiety was synthesized
and tested to evaluate their ability to inhibit Acetylcholinesterase (AChE). The most active
compounds 4 and 8, showed 85 and 69% of inhibition at 50 mM, respectively. Furthermore,
some basic SAR rules were outlined: an alkyl linker of six methylene units is the best spacer
between the carbamoyl and dibenzylamino moieties; electron-withdrawal substituents on
aromatics rings of the dibenzylamino group reduce the inhibitory power. Compound 4
produces a slow onset inhibition of AChE and this is not due to the carbamoylation of the
enzyme, as demonstrated by the time-dependent inhibition assay of AChE with compound 4
and by MALDI-TOF MS analysis of trypsinized AChE inhibited by compound 4. Instead,
compound 4 could act as a slow-binding inhibitor of AChE, probably because of its high
conformational freedom due to the linear alkyl chain
On the Inhibition of COVID-19 Protease by Indian Herbal Plants: An In Silico Investigation
COVID-19 has quickly spread across the globe, becoming a pandemic. This
disease has a variable impact in different countries depending on their
cultural norms, mitigation efforts and health infrastructure. In India, a
majority of people rely upon traditional Indian medicine to treat human
maladies due to less-cost, easier availability and without any side-effect.
These medicines are made by herbal plants. This study aims to assess the Indian
herbal plants in the pursuit of potential COVID-19 inhibitors using in silico
approaches. We have considered 18 extracted compounds of 11 different species
of these plants. Our calculated lipophilicity, aqueous solubility and binding
affinity of the extracted compounds suggest that the inhibition potentials in
the order; harsingar > aloe vera > giloy > turmeric > neem > ashwagandha > red
onion > tulsi > cannabis > black pepper. On comparing the binding affinity with
hydroxychloroquine, we note that the inhibition potentials of the extracts of
harsingar, aloe vera and giloy are very promising. Therefore, we believe that
these findings will open further possibilities and accelerate the works towards
finding an antidote for this malady
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