Cheminformatics and Computational Chemical Biology

Biography:

Hiba Zalloum is a Researcher in Hamdi Mango Center for Scientific Research at the University of Jordan. She holds a Master’s degree in Chemistry from The University of Jordan. Her practical research dealt with the synthesis, chelation and sorption properties of chelating polymers. Recently, her research interest is turning to molecular modeling and drug discovery field. She has 15 publications, 13 ISI-published articles, 2 book chapters and is now running 6 funded research projects.

Abstract:

To discover potential antitumor agents directed toward human epidermal growth factor receptor-2 HER2/ErbB2 overexpression in cancer, we have explored the pharmacophoric space of 115 HER2/ErbB2 inhibitors. This identified 240 pharmacophores which were subsequently clustered into 20 groups and cluster centers were used as 3D-pharmacophoric descriptors in QSAR analysis with 2D-physicochemical descriptors to select the optimal combination. We were obliged to use ligand efficiency as the response variable because the logarithmic transformation of bioactivities failed to access self-consistent QSAR models. Two binding pharmacophore models emerged in the optimal QSAR equation, suggesting the existence of distinct binding modes accessible to ligands within the HER2/ErbB2 binding pocket. The QSAR equation and its associated pharmacophore models were employed to screen the National Cancer Institute (NCI) and Drug Bank Databases to search for new, promising, and structurally diverse HER2 inhibitory leads. Inhibitory activities were tested against HER2-overexpressing SKOV3 Ovarian cancer cell line and MCF-7 which express low levels of HER2. In silico mining identified 80 inhibitors out of which four HER2 selective compounds inhibited the growth of SKOV3 cells with IC50 values<5 µM and with virtually no effect in MCF-7 cells. These lead compounds are excellent candidates for further optimization. Further screening on different breast cancer cells with different HER2 expression patterns has been done.

Biography:

Rhazi Naima is a PhD Student and has co-supervised thesis between the University of Pau et des Pays d’Adour (France) and University Hassan II (Morocco). Her subject in PhD entitled “Elaboration of ecological adhesives and bio-composites from Moroccan Acacia mollissima Barks”. She has a specialized Master degree in Quality Control of Food, Pharmaceutical and Cosmetics Industries and has training in Integrated Management System: Health, Quality, Safety and Environment in food alimentary and plastics center. She has given 5 oral presentations, 2 posters in international workshops and conferences and also published 2 papers in reputed journals: Industrial Crops and Products and Arabian Journal of Chemistry.

Abstract:

In order to increase the yield extraction of condensed tannins, to preserve the quality and the reactivity of phenolic compounds extracted and also to find new environmentally-friendly extraction conditions a response surface methodology (RSM) was used. This methodology was an effective and powerful statistical method to optimize extraction process while giving a maximum of information, reducing number of experimental trials required and giving the best precision of the results calculated with the established model. The development of the experimental design was described by Rhazi et al., (2015 a). RSM was used to identify the significant factors to improve yield extraction, to reduce solvent proportion and time extraction. It permit to model extraction conditions and also to determine optimal conditions, which give higher yield of condensed tannins using lower proprtion of solvent and shorter time extraction. The present study aims to develop green extraction process of phenolic compounds extracted from Moroccan barks of Acacia mollissima using a traditional maceration. The parameters studies in this research are time extraction (X1), methanol proportion (X2) and bark ages (X3). The result of RSM showed a good agreement between the predicted and experimental values (R2= 0.98; 0.97 and 0.99 respectively for the extracts).

Biography:

Ouahab Ammar has completed his PhD from China Pharmaceutical University. He is an Assistant Professor in the Department of Pharmacy at Batna University. He has succefully developed a novel oral delivery system of indomethacin for Roche-Hoffman when he was a Master’s student. He has been active in research on new smart drug delivery systems and has published 12 papers in reputed journals.

Abstract:

It is somehow easy to understand why it is still so controversial the mechanisms of cellular uptake of Cell-Penetrating Peptides (CPP). Although there is evidence that these peptides are capable of directly crossing the plasma membrane without any intermediate step, still several researchers claim that endocytosis is an intermediate step required for entry into the cells. It is well known that ionic interactions play a critical role for the binding to the plasma membrane and translocation of CPPs. A simulation of the interaction between arginine-glycine (RG)5 and histidine-glutamic acid (HE)5, as well as with DOPC of the lipid bilayer was conducted in order to calculate the free binding energy. The results supported the data obtained in the in vitro release, cell uptake and cytotoxicity studies. The absolute value of binding energy of (RG)5 with (HE)5 was the highest. However, a decrease in the pH was found to diminish this strong bond. Interestingly, the conjugation of (RG)5 to PEG-PLA copolymer increased the binding energy to DOPC. In summary, the peptides tend to interact with the cell membrane which facilitates the uptake in an energy and receptor independent manner as postulated by many researchers.

Biography:

Abstract:

Our research group has created a new strategy for phylogenenomic constructions. This procedure is free of the errors associated to sequence alignments and, for bacteria, uses as homologous characters, shared and distinctive 21-mers located in any of both DNA strands and, having identical sequences or single base substitutions when shared. Two, intellectually protected components, are used for this purpose. The Virtual Analysis Method for Phylogenomic fingeRprint Estimation (VAMPhyRE) and the VAMPhyRE Probe Set (VPS). For bacteria, VPS-13 is used, which is constituted by 15,264 13-mer sequences, which were selected from all the 67,108.864 13-mer possible sequences, by shuffling, and extracting those sequences having 35-65% GC, high sequential entropy and at least two internal and spaced sequence differences. VAMPhyRE selects the 21-mer homologous sequences using a three step procedure. First searches genomic 13-mer sequences having identical or single target/probe differences. Then takes each 13-mer target sequence found by one probe, and extends it to 21-mer, by adding the 4 bases located at both flanks in the respective targets. These are the virtual genomic fingerprints (VGF). Finally it compares each of the 21-mer sequences present in one strain with the 21-mer sequences found by the same probe in the other strains to mark them as shared, when they have at least 19 identities, or distinctive homologous hits. This information is used to calculate distance scores and to construct the phylogenomic trees. This strategy has been successfully applied to Bacillus anthracis, Mycobacterium and other Actinomycetes. Since the genomic 21-mers found under our strategy correspond to conserved sequences they have key molecular roles, such as transport, catalysis, production of energy, regulation, biosynthesis, etc. and therefore, they perform essential biological roles such as, the capability to grow in different environments or hosts, to cause disease, or to produce substances of interest. Therefore, these VGF are a source of sequences which in combination with the respective phylogenomic tree, the genomic databases and the biological properties, can be used for diverse biotechnological applications such as diagnostics, metagenomic analysis, resistance, virulence, markers of strains of industrial interest, etc. We currently are working in data mining of this information. The following scheme illustrates the information included in the previous abstract.

Biography:

Dr Bin Thani graduated with a BSc degree from The University of Bahrain, Kingdom of Bahrain in 1998. He completed his Master study on Medical Biotechnology from the Arabian Gulf University, Kingdom of Bahrain. In 2004, he started his PhD study under the supervision of Dr Kumar Rajakumar from the University of Leicester, UK. His research project in the PhD had involved in silico analysis of bacterial DNA sequences and the use of different bioinformatic approaches (e.g., tRNAcc and MobilomeFINDER) to elucidate possible functions for novel DNA sequences.

Abstract:

After completing its sequence/annotation in 2005, Magnetospirillum magneticum AMB-1 had become one of the most important magnetotactic genomes used to facilitate analysis of the magnetosome formation process. In this paper we investigate the genome contents of AMB-1 and other magnetotactic bacteria to demonstrate the size of mobile genome and number of conserved genes in M. magneticum AMB-1. The preliminary analysis presented here shows the mosaic structure of these genomes. 100 genomic islands were identified in AMB-1 by IslandPick. Moreover, the size of AMB-1 magnetosome island (MAI), previously known to be 100 kb, was re-estimated to be in the size range of 110 kb. Thus more genes were included to be part of this GI. The investigation included the use of comparative approaches to elucidate conserved protein coding sequences. 13 CDS were identified to be conserved among three magnetotactic genomes. One CDS (amb3135) was conserved in five magnetotactic genomes. The amino acid sequence for this CDS (amb3135) was used to draw a phylogenetic tree among magnetotactic bacteria. The phylogeny based on amb3135 is in concordance with previous studies indicating a close relationship between strain AMB-1 and other Magnetospirillum species

Biography:

Dr. A.K. Saxena, is actively involved in the domain of Medicinal Chemistry & CADD, drug discovery and development research. He has 45 years of research experience with 200 research publications, 19 reviews/articles in books and/monographs, 72 patents and has delivered >180 invited lectures, chaired >45 sessions. He is Fellow of Royal Society of Chemistry, UK, Editorial Board Member of different prominent journals like, Medicinal Chemistry Research, SAR and QSAR in Environmental Research, online International journal ARKIVOC, and Patent Evaluator: Current Drugs, U.K. He is also series editor for book series “Topics in Medicinal Chemistry” published by Springer Verlag.

Abstract:

In recent years tuberculosis (TB) chemotherapy is dependent on drugs targeting bacterial metabolism with bactericidal action having no effect on dormant or latent or metabolically inactive bacilli that target cell division. The ATP synthase is a ubiquitous enzyme in energy metabolism due to its involvement in the generation of sufficient amount of ATP and/or in generating a proton motive force (PMF) in mycobacteria during adverse conditions of low oxygen environment and nutrient deficiency. This pivotal role of ATP synthase is targeted by the diarylquinoline TMC207 that kills Mycobacterium tuberculosis. Utilizing the state-of-the-art medicinal chemistry approach the quinoline class of aryl-sulfonamides has been identified as potent, orally bioavailable and selective mycobacterial ATP synthase inhibitors. Among a series of compounds synthesized which were effective in vitro on ATP synthase, the lead compound [N-(7-chloro-2-methylquinolin-4-yl)-N-(3-((diethylamino)methyl)-4-hydroxyphenyl)-2,3-dichlo-r obenzene sulfonamide] exhibited excellent selectivity (mycobacterium ATPase IC50 = 0.51 µM, mammalian ATPase IC50 >100 µM, and selectivity >200) and is also active in the hypoxic culture of non replicating M. tuberculosis at 100 µg/mL (32-fold of its MIC) as compared to positive control isoniazid [approximately 0.2 log10 reduction in CFU at 5 lg/mL (50-fold of its MIC)]. Docking of the best compound on homology modeled ATP synthase revealed the participation of the protonated tertiary amine and hydroxyl group to interact with the carboxylate oxygen of Glu61 that is similar to TMC207. The study provides a deep understanding about the structural requirements for ATP synthase inhibitors helpful in the discovery of novel chemical entities.

Biography:

Abstract:

Herein, we report the synthesis of ruthenium(II) hydride carbonyl complex containing benzoyl pyridine as a co-ligand. The complex has been examined for C, H, N elemental analysis, infrared and UV-Visible spectroscopy including the determination of decomposition temperature and cyclic voltammetry as well. Moreover, Gaussian 09W software package has been employed to carry out the quantum chemical studies. Triphenylphosphine (Tpp), Benzoyl Pyridine (bpy) and the [RuHCl(CO)(bpy)(Tpp)] complex have been separately optimized at the reliable level of theory using ab initio, semi-empirical and DFT methods. AM1 and PM6 have been applied for ligands and the complex, respectively. HF level of theory, AM1/PM6 and DFT based simulated frequencies have been manipulated to arrive at the computational thermo chemistry and energetics of the involved compounds. The DFT calculations with Becke-3–Lee–Yang–Parr (B3LYP)/6-31G and B3LYP/LANL2DZ combinations were used. TD-DFT speculation has also been introduced to infer the CO-releasing ability in the target compound and has been proven as an effective CO releaser at the cost of visible range of electromagnetic radiation. In vitro cell viability tests against COLO-205 human cancer cells have also been carried out with regard to the complex. MTT based cell toxicity studies of [RuHCl(CO)(PPh3)3] and [RuHCl(CO)(bpy)(PPh3)], have revealed the model complex as an excellent anticancer agent. From IC50 values of 53 in case of former and of 40 in the later, it establishes that latter bears more antiproliferative potential.

Biography:

Dr‘ Nuzhat Gull has completed her PhD from A.M.U‘ Aligarh at the age of 30 years and has served as a Research Associate at University of Kassmir, Srinagar-India. She has published 12 articles in reputed journals and is presently working as an Asst. Prof‘ In Dept‘ of Chemistry,Govt Degree College for Women,MA Road, Srinagar‘

Abstract:

In the present study the cationic gemini surfactant assisted refolding of guanidinium hydrochloride (GndHcl) denatured mammalian serum albumins viz. sheep serum albumin (SSA), rat serum albumin (RSA) and porcine serum albumin (PSA) using a combination of cationic gemini surfactants, pentanediyl-a,w-bis(cety|dimethylammonium bromide (C16H33(CH3)2N+—(CH2)5—N+(CH3)2C16H33).2Br-designated as GS and methyl- [3-cyclodextrin in the artificial chaperone assisted two step method, is attempted The studies were carried out in an aqueous medium (pH 7‘4) using dynamic light scattering (DLS), circular dichroism (CD), and fluorescence spectroscopy‘ A perusal of DLS data indicates that against the native hydrodynamic radius (Rh) of 43 nm in SSA, 3.9 nm in PSA and 35 nm in RSA, the Rh of the said proteins, when refolding is attempted by simple dilution, increases to 217nm, 36.6 nm and 372 nm, respectively‘ Hydrodynamic radii very near to the native protein, Le, 40 nm, 41 nm and 4.4 nm for RSA, PSA and SSA respectively, is obtained on the sequential addition of GS and methyl-B-cyclodextrin to the denatured protein. Circular dichroism studies corroborate with the DLS data. The results obtained from the multi-technique approach are ascribed to the presence of two charged head-groups and two hydrocarbon tails in the gemini surfactants resulting in very strong electrostatic and hydrophobic interactions Based on the present study it is suggested that gemini surfactants may be utilized in the protein refolding studies and thus may address one of the most pressing demand of biotechnology industry for the development of efficient and inexpensive folding aides.

Biography:

Abstract:

Nitric oxide was first discovered as a colorless, toxic gas in 1772 by Joseph Priestly. Unfortunately, the tag of toxic gas and air pollutant continued until 1987, when it was shown to actually be produced naturally in the body. By 1987, nitric oxide’s role in regulating blood pressure and relieving various heart ailments became well-established. Very recently, researches revealed that nitric oxide is used by macrophages to kill tumor cells and bacteria. In 1992, nitric oxide was voted ‘Molecule of the Year’. The importance of the molecule became front page news in 1998 when Louis J Ignerro, Robert F Furchgott and Ferid Murad were awarded the Nobel Prize for Medicine and Physiology for identifying nitric oxide as a signaling molecule. The discovery has opened up newer ways of treatment for millions of patients. Endogenously produced by the enzyme NO Synthase (NOS), NO has been found to be an essential component in many physiological processes, such as cytotoxicity, neural-transmission and blood pressure regulation, and dysfunction in NO metabolism has been associated in a number of disease states, such as epilepsy, arthritis, diabetes, hypertension, and septic shock. In particular, the so-called NO donor drugs could have an important therapeutic effect on the treatment of many cardiovascular diseases such as angina pectoris (chest pain) and hypertension. The organic nitrate and nitrite esters, including nitroglycerin, amyl nitrite, isosorbide dinitrate and nicorandil, have been used in the treatment of cardiovascular diseases for many years. Unfortunately, the development of tolerance to these compounds limits its use as NO donor. Current interest in exogenous NO-donor drugs has focused on the design and synthesis of new drugs with improved pharmacokinetic properties. The search for new storage release systems, capable of delivering NO to desired targets, has stimulated the chemistry of metal nitrosyl complexes. Catalytic applications of transition metal nitrosyl complexes are of current interest to organometallic and organic chemists. Another stimulus to investigating NO reactivity of metal nitrosyl complexes, has been the developments in pollution control, largely stemming from attempts to remove, or at least diminish the concentration of NO in exhaust gases emitted by the internal combustion engine. Certain dinitrosyl complexes of transition metals were found to catalyze the conversion of CO and NO to the less harmful gases CO2 and N2O, which is of intrinsic interest because of their environmental relevance. In recent years, CO has also been shown to play a key role in human physiology. Depending upon its concentration CO molecule exhibits distinct physiological or pathological effects. CO releasing molecules have shown promises in controlling tissue damage. Hence, search for new and effective CO donors for controlled delivery to biological targets is of utmost importance. In view of above, this talk, therefore, primarily focuses our recent work related to the synthesis, characterization and quantum mechanical DFT computational studied of some recently reported metal nitrosyls and carbonyls form our laboratory. For making this talk interesting, this presentation will begin with basics of nitrosyl and carbonyl chemistry along with scope of these compounds in the beneficial role of mankind.

Biography:

Ahmed Haroun has completed his PhD at the age of 28 years from University of Tokyo in Mechanical Engineering, He is currently a postdoctoral research fellow at National University of singapore (NUS), and holding the position of lecturere assistant at Cairo University. His research interests include energy harvesting for implantable and wearable devices; MEMS-based energy harvesting; MEMS sensors and actuators, Implantable bio-MEMS; Vibration energy harvesting; Dynamics of multibody systems.

Abstract:

Self-powering of wireless sensors and wireless micro devices attract the attention of many researches nowadays. Problems associated with chemical batteries such as limited life time and minimization restrictions can be solved using the approach of energy harvesting. Various ambient energy sources such as vibration, thermal, light, wind, etc. could be harvested and converted into electrical energy. However, vibration energy harvesting is more convenient for important kinds of applications such as machine condition monitoring, where sensors are plased in a deep dark place, and human body-powered devices whether they are wearable or implantable. Some problems arise when dealing with human motion energy harvesting. Human body provides a kind of unsteady low frequency vibrations which are difficult to matched by most common resonant harvesters. Instead, a way of non-resonant low frequency energy harvesting should be used. In this speech, a micro electromagnetic non-resonant energy harvester based on free/impact motion will be presented. Free relative motion is allowed between tube-carrying an electrical coil directly connected to the vibration source and a permanent magnet inside. Impacts appear between the magnet and two hard end stops. Free motion enhances power harvesting at low frequency, while combined free/impact motion results in a non-resonant behavior in which the output power increases with input amplitude and/or frequency. In addition, the harvester has a simple construction which allows fabrication with small sizes. Hence, the harvester can be well suited for small size applications encountered variable large amplitude – low frequency vibrations such as human powered devices.

Biography:

Muthukumarasamy Karthikeyan obtained his Bachelors and Masters Degree in Chemistry from Pondicherry University and Ph.D. (Chemistry) from National Chemical Laboratory (University of Pune) in the area of Organic Synthesis. He joined CSIR -National Chemical Laboratory, Pune as a senior scientist in the year 2000 and since then he is pursuing his active research career in Chemoinformatics especially in the area of high performance computing for molecular informatics and its application in lead identification and lead discovery. He is also the recipient of BOYSCAST Fellowship from Department of Science and Technology, and Long term Overseas Associateship from Department of Biotechnology to conduct research in the area of molecular informatics and structure-activity relationship studies at University of North Carolina at Chapel Hill, USA. His current interest includes development of open-source tools for virtual screening in drug discovery and he recently published ten consecutive research articles on this theme. Other important areas of research in molecular informatics includes structure-activity relationships, molecular dynamics simulation, Chemical Reaction Modeling and in visual computing for molecular informatics (ChemRobot), hybrid computing (distributed, parallel, cloud) using multicore CPU-GPU processors as a web-based problem solving environment in chemical informatics.

Abstract:

Virtual screening is an indispensable tool to cope with the massive amount of data being tossed by the high throughput omics technologies. With the objective of enhancing the automation capability of virtual screening process a robust portal termed MegaMiner has been built using the cloud computing platform wherein the user submits a text query and directly accesses the proposed lead molecules along with their drug-like, lead-like and docking scores. Textual chemical structural data representation is fraught with ambiguity in the absence of a global identifier. We have used a combination of statistical models, chemical dictionary and regular expression for building a disease specific dictionary. To demonstrate the effectiveness of this approach, a case study on malaria has been carried out in the present work. MegaMiner offered superior results compared to other text mining search engines, as established by F score analysis. A single query term 'malaria' in the portlet led to retrieval of related PubMed records, protein classes, drug classes and 8000 scaffolds which were internally processed and filtered to suggest new molecules as potential anti-malarials. The results obtained were validated by docking the virtual molecules into relevant protein targets. It is hoped that MegaMiner will serve as an indispensable tool for not only identifying hidden relationships between various biological and chemical entities but also for building better corpus and ontologies.

Biography:

Rhazi Naima is a PhD Student and has co-supervised thesis between the University of Pau et des Pays d’Adour (France) and University Hassan II (Morocco). Her subject in PhD entitled “Elaboration of ecological adhesives and bio-composites from Moroccan Acacia mollissima Barks”. She has a specialized Master degree in Quality Control of Food, Pharmaceutical and Cosmetics Industries and has training in Integrated Management System: Health, Quality, Safety and Environment in food alimentary and plastics center. She has given 5 oral presentations, 2 posters in international workshops and conferences and also published 2 papers in reputed journals: Industrial Crops and Products and Arabian Journal of Chemistry.

Abstract:

Response surface methodology (RSM) was an effective and powerful statistical method to optimize the extraction process while giving a maximum of information, reducing the number of experimental trials required and giving the best precision of the results calculated with the established model. The experimental design used permit to determine the factors which had a dominating influence on the required properties, to choose the favorable levels of certain factors, to model the response using a mathematical model and also to optimize the multi-criteria of the process. In this study, we used this methodology to optimize extraction process of poly-phenols and tannins extracted by microwave from Moroccan barks of Acacia mollissima. The variables studied are: time extraction (X1), methanol proportion (X2) and microwave power (X3). The responses measured were: poly-phenols yields (Y1) and condensed tannins yield (Y2). The results of this study were evaluated with colorimetric assays. A face-centered composite design (FCCD) was applied to evaluate the effects of these variables on the phenolic compounds contents. RSM applied in microwave assisted extraction, permitted to develop green extraction process of poly-phenols and tannins extracted, using lower microwave power and methanol proportion with a shortest time extraction and in the same time improve the quantity of extractives obtained from renewable natural resource.

Biography:

Abstract:

Coumarins such as [1], a natural product secluded from the Australian plant Leionema ellipticum, P. G. Wilson (Rutaceae), or the simple unsubstituted coumarin [2], were detected to act as effective inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1)[1−3]. Substituted coumarin such as sulfocoumarins (1,2-benzoxathiine 2,2-dioxides) possessing are the most important[4] class of Potent and Isoform-Selective Inhibitors of Tumor-Associated Carbonic Anhydrases CA IX[4]. I have attempted to build QSAR models using the OMEGA, MOPAC, PRECLAV, DRAGON and BROOD software to explore the correlations between the calculated molecular descriptors on the pool of 16 compounds and their experimental CAIX inhibitory activities. The quality of prediction is high enough (SE =0 .1680, r2=0 .9483; F 128.4198, Q= 8539). The virtual molecular fragment that lead to a significant increase of the inhibitor activity of hCA IX is C2HN3 , The virtual fragments , Br atom and NO2 leads to a significant decrease of the inhibitor activity value. The innovation of this work consists in not only exploring the structural attributes of bioactive molecules but in predicting in silico the structures of eleven new compounds which may show Tumor-Associated Carbonic Anhydrases IX (CAIX) inhibitory activity. The analogs of the lead molecule are generated by replacing selected fragments that have similar shape and electrostatics. The various pharmacokinetic evaluations and synthetic accessibility test were also carried out to search more suitable compounds. The molecules of the prediction set include many molecules having high computed activity.