Articles 2016

Articles 2016

Subcritical hydrothermal pretreatment of olive mill solid waste for biofuel production

HibaAbu Tayeh, Odelia Levy-Shalev, HassanAzaizeh, Carlos G.Dosoretzb

Bioresource Technology, Volume 199, January 2016, Pages 164-172 rights and conten


The hydrothermal pretreatment of olive mill solid waste amended with 0.6 M organic acids was studied at temperatures between 100 and 170 °C. Acetic and formic acids which are endogenous intermediates of hemiacetyl splitting at subcritical conditions were tested. Formic acid, with smaller molecular size and lower pKa, was found to be more effective than acetic in the entire range of temperatures tested. Yield of enzymatic hydrolysis was significantly enhanced (>2 folds) at temperatures above 140 °C. Concentration of aldehyde byproducts in the medium increased with temperature and pressure and addition of organic acids, however, the highest concentration detected (ca 1 g/L) did not surpass values reported as inhibitory of sugars fermentation to ethanol by either yeast or bacteria. Aldehyde production was more affected by temperature than by acid addition. Concluding, addition of formic acid to hydrothermal pretreatment at relatively mild temperatures (140–170 °C) and pressure (10–13 atm) improved saccharification yield while saving energy.


Modeling Ensembles of Loop Conformations by Iterative Stochastic Elimination

Amit Michaeli, Anwar Rayan.

Journal Name: Letters in Drug Design & Discovery, Volume 13 , Issue 7 , 2016

DOI : 10.2174/1570180813666160617103437


Protein models are useful in structure-based protein engineering applications, including designing drugs, redesigning enzyme specificity, and designing new folds in proteins. Predicting loop structures is considered the main challenge in protein 3-D structure modeling. The flexibility of loop regions dictates the need for special attention to their conformations. In this paper, we report on the implementation of iterative stochastic elimination (ISE) optimization technology for the ab initio modeling of protein variable regions (loops). The ISE algorithm was tested on a benchmark of 70 structurally refined loops. The median root-mean-square deviation (RMSD) of the loop residues was 1.5Å, with 80% of the targets conforming to the native with RMSD lower than 2.0Å. The median-backbone, heavy-atom global RMSD of the loop predictions were 0.67Å for short loops (4-6 residues), 0.88Å for medium loops (7-9 residues), 1.68Å for long loops (10-12 residues) and 2.76Å for very long loops (13-16 residues). In addition to the accurate modeling of short, medium and long loops, the current method provided us with ensembles of conformations, which are crucial for studying the dynamic nature of loops, mainly on the surfaces of proteins. The proposed technique could be incorporated into modules for generating homologybased models and for flexible docking.


How to Choose the Suitable Template for Homology Modelling of GPCRs: 5-HT7 Receptor as a Test Case

Nir Shahaf, Matteo Pappalardo, Livia Basile, Salvatore Guccione, Anwar Rayan

First published: 28 June 2016

DOI: 10.1002/minf.201501029  View/save citation


G protein-coupled receptors (GPCRs) are a super-family of membrane proteins that attract great pharmaceutical interest due to their involvement in almost every physiological activity, including extracellular stimuli, neurotransmission, and hormone regulation. Currently, structural information on many GPCRs is mainly obtained by the techniques of computer modelling in general and by homology modelling in particular. Based on a quantitative analysis of eighteen antagonist-bound, resolved structures of rhodopsin family “A” receptors – also used as templates to build 153 homology models – it was concluded that a higher sequence identity between two receptors does not guarantee a lower RMSD between their structures, especially when their pair-wise sequence identity (within trans-membrane domain and/or in binding pocket) lies between 25 % and 40 %. This study suggests that we should consider all template receptors having a sequence identity ≤50 % with the query receptor. In fact, most of the GPCRs, compared to the currently available resolved structures of GPCRs, fall within this range and lack a correlation between structure and sequence. When testing suitability for structure-based drug design, it was found that choosing as a template the most similar resolved protein, based on sequence resemblance only, led to unsound results in many cases. Molecular docking analyses were carried out, and enrichment factors as well as attrition rates were utilized as criteria for assessing suitability for structure-based drug design.



Salvatore Guccione, Matteo Pappalardo, Martha E. Leonardi, Anwar Rayan.

Article in Inflammation Research 65(S1):S44 · July 2016 with 6 Reads

Cite this publication


Histamine receptors belong to class A GPCRs, rhodopsin type family. To date, four histamine receptors are known to be activated by the same endogenous agonist (histamine) and implicated in various diseases. From a quantitative analysis of eighteen receptors and subsequently derived 153 pairs of data, we came to the conclusion that higher sequence identity between two receptors does not guarantee lower root mean square deviations (RMSD) between their structures, especially when pair-wise sequence identity lies between 25 and 40 %. This finding is somehow not in agreement with the well accepted criterion of choosing as a template the homologous protein with the highest sequence similarity, especially if the query protein shares higher than 30 % sequence identity with the template sequence. Our findings suggest that receptors having less than 50 % sequence identity should be considered and evaluated since correlation is lacking in this range. Additionally, when testing suitability for structure-based drug design, we found that choosing the template protein based on the most similar sequence resemblance only is not justified. Performance in molecular docking may be taken into account in order to determine which of the obtained models is likely to be utilized and mainly based on the enrichment factor criterion. Correlations between enrichment factors and pair-wise sequence identity of the various models will be discussed. The H1–H4 receptors’ models which were constructed based on the 18 templates will be described and their efficacy in discriminating between actives and non-actives was reported


In silico modeling techniques for predicting the tertiary structure of human H4 receptor. 

Zaid H ,  Raiyn J ,  Osman M ,  Falah M ,  Srouji S ,  Rayan A .

Frontiers in Bioscience (Landmark Edition) [01 Jan 2016, 21:597-619]

Type: Research Support, Non-U.S. Gov’t, Review, Journal Article

DOI: 10.2741/4409  The Digital Object Identifier (DOI) System enables identification of digital entities


First cloned in 2000, the human Histamine H4 Receptor (hH4R) is the last member of the histamine receptors family discovered so far, it belongs to the GPCR super-family and is involved in a wide variety of immunological and inflammatory responses. Potential hH4R antagonists are proposed to have therapeutic potential for the treatment of allergies, inflammation, asthma and colitis. So far, no hH4R ligands have been successfully introduced to the pharmaceutical market, which creates a strong demand for new selective ligands to be developed. in silico techniques and structural based modeling are likely to facilitate the achievement of this goal. In this review paper we attempt to cover the fundamental concepts of hH4R structure modeling and its implementations in drug discovery and development, especially those that have been experimentally tested and to highlight some ideas that are currently being discussed on the dynamic nature of hH4R and GPCRs, in regards to computerized techniques for 3-D structure modeling.

 Identification of a New Antibacterial Sulfur Compound from Raphanus sativus Seeds

Jeries JadounAhmad YazbakSalwa RushrushAmira Rudy, and Hassan Azaizeh.

Evidence-Based Complementary and Alternative Medicine, Volume 2016 (2016), Article ID 9271285, 7 pages


Raphanus sativus L. (radish), a member of Brassicaceae, is widely used in traditional medicine in various cultures for treatment of several diseases and disorders associated with microbial infections. The antibacterial activity of the different plant parts has been mainly attributed to several isothiocyanate (ITC) compounds. However, the low correlation between the ITC content and antibacterial activity suggests the involvement of other unknown compounds. The objective of this study was to investigate the antibacterial potential of red radish seeds and identify the active compounds. A crude ethanol seed extract was prepared and its antibacterial activity was tested against five medically important bacteria. The ethanol extract significantly inhibited the growth of all tested strains. However, the inhibitory effect was more pronounced against Streptococcus pyogenesand Escherichia coli. Bioassay-guided fractionation of the ethanol extract followed by HPLC, 1H-NMR, 13C-NMR, 15N-NMR, and HMBC analysis revealed that the active fraction consisted of a single new compound identified as [5-methylsulfinyl-1-(4-methylsulfinyl-but-3-enyl)-pent-4-enylidene]-sulfamic acid, which consisted of two identical sulfur side chains similar to those found in ITCs. The minimal inhibitory concentration values of the isolated compound were in the range of 0.5–1 mg/mL. These results further highlight the role of radish as a rich source of antibacterial compounds.

Evidence-Based Complementary and Alternative Medicine
Volume 2016 (2016), Article ID 9271285, 7 pages