Attracting cavities for docking. Replacing the rough energy landscape of the protein by a smooth attracting landscape.

Molecular docking is a computational approach for predicting the most probable position of ligands in the binding sites of macromolecules and constitutes the cornerstone of structure-based computer-aided drug design. Here, we present a new algorithm called Attracting Cavities that allows molecular docking to be performed by simple energy minimizations only. The approach consists in transiently replacing the rough potential energy hypersurface of the protein by a smooth attracting potential driving the ligands into protein cavities. The actual protein energy landscape is reintroduced in a second step to refine the ligand position. The scoring function of Attracting Cavities is based on the CHARMM force field and the FACTS solvation model. The approach was tested on the 85 experimental ligand-protein structures included in the Astex diverse set and achieved a success rate of 80% in reproducing the experimental binding mode starting from a completely randomized ligand conformer. The algorithm thus compares favorably with current state-of-the-art docking programs

Synthesis and characterization of Polyindole and its catalytic performance study as a heterogeneous catalyst

The catalytic performance study of polyindole as a heterogeneous catalyst is reported for the synthesis of 3,3'-arylmethylene-bis-1H-Indole derivatives using various substituted aldehydes and indole under reflux reaction condition with good to excellent yield. Polyindole was synthesized by chemical oxidative polymerization using citric acid as a dopant. The synthesized polymer was well characterized by various spectroscopic techniques like FT-IR, XRD, FESEM, etc. The XRD pattern confirms the partially crystalline nature of polyindole. The FESEM images of polyindole revealed the formation of irregularly shaped particulate nature with size in the range of 0.2 to 6 micron. In FT-IR spectrum, the major peak at similar to 3400 cm(-1) indicates N-H stretching and at 1564-1624 cm(-1) indicates C-C stretching of benzenoid ring of indole. The presence of peak at similar to 3400 cm(-1) indicates that the polymerization does not occur at nitrogen. The present protocol has certain advantages like recyclability, low loading of the catalyst, low-cost and efficient use of polyindole as a heterogeneous catalyst

Phytochemical Characterization, Antioxidant and Anti-Proliferative Properties of Rubia cordifolia L. Extracts Prepared with Improved Extraction Conditions

none11sìRubia cordifolia L. (Rubiaceae) is an important plant in Indian and Chinese medical systems. Extracts prepared from the root, stem and leaf have been used traditionally for the management of various diseases. Some of the known effects are anti-inflammation, neuroprotection, anti-proliferation, immunomodulation and anti-tumor. A comparative account of the extracts derived from different organs that lead to the identification of the most suitable solvent is lacking. We explored the presence of phytochemicals, antioxidant activity and anti-proliferative properties of a variety of solvent-based extracts of root, and methanol extracts of stem and leaf of R. cordifolia L. The antioxidant potential was determined by DPPH, hydrogen peroxide, nitric oxide and total antioxidant assays. The anti-proliferative nature was evaluated by MTT assay on HeLa, ME-180 and HepG2 cells. The composition of the extracts was determined by UPLC-UV-MS. We found that the root extracts had the presence of higher amounts of antioxidants over the stem and leaf extracts. The root extracts prepared in methanol exhibited the highest cytotoxicity in HepG2 cells. The main compounds identified through UPLC-UV-MS of the methanol extract give credibility to the previous results. Our comprehensive study corroborates the preference given to the root over the stem and leaf for extract preparation. In conclusion, we identified the methanol extract of the root to be the most suited to have bioactivity with anti-cancer potential.Humbare, Ravikiran B; Sarkar, Joyita; Kulkarni, Anjali A; Juwale, Mugdha G; Deshmukh, Sushil H; Amalnerkar, Dinesh; Chaskar, Manohar; Albertini, Maria C; Rocchi, Marco B L; Kamble, Swapnil C; Ramakrishna, SeeramHumbare, Ravikiran B; Sarkar, Joyita; Kulkarni, Anjali A; Juwale, Mugdha G; Deshmukh, Sushil H; Amalnerkar, Dinesh; Chaskar, Manohar; Albertini, Maria C; Rocchi, Marco B L; Kamble, Swapnil C; Ramakrishna, Seera

Computational Treatment of Metalloproteins

Metalloproteins present a considerable challenge for modeling, especially when the starting point is far from thermodynamic equilibrium. Examples include formidable problems such as metalloprotein folding and structure prediction upon metal addition, removal, or even just replacement; metalloenzyme design, where stabilization of a transition state of the catalyzed reaction in the specific binding pocket around the metal needs to be achieved; docking to metal-containing sites and design of metalloenzyme inhibitors. Even more conservative computations, such as elucidations of the mechanisms and energetics of the reaction catalyzed by natural metalloenzymes, are often nontrivial. The reason is the vast span of time and length scales over which these proteins operate, and thus the resultant difficulties in estimating their energies and free energies. It is required to perform extensive sampling, properly treat the electronic structure of the bound metal or metals, and seamlessly merge the required techniques to assess energies and entropies, or their changes, for the entire system. Additionally, the machinery needs to be computationally affordable. Although a great advancement has been made over the years, including some of the seminal works resulting in the 2013 Nobel Prize in chemistry, many aforementioned exciting applications remain far from reach. We review the methodology on the forefront of the field, including several promising methods developed in our lab that bring us closer to the desired modern goals. We further highlight their performance by a few examples of applications

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Bipolar Hosts Based on a Rigid 9,10-Dihydroanthracene Scaffold for Full-Color Electrophosphorescent Devices

[[sponsorship]]原子與分子科學研究所[[note]]已出版;[SCI];有審查制度;具代表性[[note]]http://gateway.isiknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Drexel&SrcApp=hagerty_opac&KeyRecord=0021-2148&DestApp=JCR&RQ=IF_CAT_BOXPLO

Synthesis and screening of 1, 3, 4-oxadiazinoindolinone and <i>s</i>-triazole derivatives of pyranobenzopyran

1465-14693-Formyl-4- hydroxycoumarin is treated with malonic acid in the presence of zinc chloride catalyst to give 2H, 5H-2,5-dioxo-3-pyrano[3, 2-c]benzopyranoic acids 1a-d which on treatment with methanol in the presence of thionyl chloride give methyl 2H, 5H-2,5-dioxopyrano[3, 2-c]benzopyran-3-oates 2a-d. Compounds 2a-d were converted into their acid hydrazides 3a-d. 3a-d on treatment with isatin yield 1H, 2H-3-(2H, 5H-2,5-dioxopyrano[3, 2-c]benzopyran-3-carboxyhydrazono)-2-indolinones 4a-d which on cyclisation with conc. H2SO4 afford 3-[1, 3, 4-oxadiazino[5, 6-b]indol-2-yl]-2,5-dioxopyrano[3,2-c]benzopyrans 5a-d. Acid hydrazides 3a-d on treatment with carbon disulfide in 10% KOH at room temperature followed by treatment with ortho-chlorobenzoic acid hydrazide furnish 3-(2H, 5H-2, 5-dioxopyrano[3, 2-c]benzopyran-3-yl)-4-{N-2'-chlorophenylcarboxamido]-5-mercapto-1,2,4-triazoles 6a-d

Development of Planter Foot Pressure Distribution System Using Flexi Force Sensors

Diabetes brings with it neurovascular complications, which results in development of high pressure areas. Patients with diabetic polyneuropathy often lose pain and temperature sensations in their feet, resulting in inadequate information about pressure under the feet, during walking or standing. This may cause injury in the feet; at times accidentally, painless trauma develops and results in ulceration. Repetitive injury may also produce bone changes, causing the foot to become deformed. It is thus very important to locate such areas using pressure distribution measurement system. A detailed study of the pressure distribution on the sole of the foot in static position is carried out. In this paper the low cost planter foot pressure system is developed to measure foot pressures in normal subjects and diabetic patients. These pressure profiles i.e. pressure concentrations can assist in writing proper orthotic prescriptions. Pressure profile of 37 diabetic and 33 normal subjects is analyzed. The initial results indicate pressures in range of 50 to 400 KPa for normal subject, higher pressures i.e. above 600 KPa at metatarsal heads for diabetic patients