Day 15 :
- Systems and Synthetic Biology | Biochemistry and Enzymology |Antibody Engineering & Therapeutics | Pharmaceutical Biochemistry | Mass Spectrometry in Proteomics |Computational Systems Biology
Location: Colombard
Session Introduction
Hailong An
Hebei University of Technology, China
Title: Identification of the calcium-dependent gating and targeted-drug discovery of calcium-activated chloride channels
Time : 14:00-14:30
Biography:
Hailong An received his PhD degree in Biophysics in Hebei University of Technology in 2005. After that, he was appointed to the faculty in Institute of Biophysics, Hebei University of Technology. From 2006 to 2008, he worked in Hebei Medical University under supervision by Prof. Hailin Zhang as a postdoc. Awarded by China Scholarship Council, he spent 20 months in Prof. Diomedes E. Logothetis’ Lab as a visiting scholar. He focuses on understanding the structure-function relationship of ion channels, the relationship between ion channels and major diseases and drug screening targeting at ion channels. More than 50 papers have been published in academic journals such as Scientific Reports, Journal of Biological Chemistry, British Journal of Pharmacology etc., and more than 40 papers were included in the SCI (total impact factor: 126.52), the paper was cited more than 200 times.
Abstract:
Calcium-activated chloride channels (CaCCs) play vital roles in a variety of physiological processes. Transmembrane protein 16A (TMEM16A) has been confirmed as the molecular counterpart of CaCCs which greatly pushes the molecular insights of CaCCs forward. However, the detailed mechanism of Ca2+ binding and activating the channel is still obscure. To identify the calcium binding site, the authors presented a computational approach which combined the fragment homology modeling with molecular dynamics simulation. Our data show that the first intracellular loop serves as a Ca2+ binding site including D439, E444, and E447. The experimental results indicate that a novel residue, E447, plays a key role in Ca2+ binding. Compared with WT TMEM16A, E447Y produces a 30-fold increase in EC50 of Ca2+ activation and leads to a 100-fold increase in Ca2+ concentrations that is needed to fully activate the channel. It is well established that TMEM16A is a drug target in many diseases, including cystic fibrosis, hypertension, asthma, and various tumors. Therefore, identifying potent and specific modulators of the TMEM16A channel is crucial. Here, the authors identified two modulators from the traditional Chinese medicine, an activator, Ginsenoside Rb1 (GRb1) which can increase the amplitude and frequency of contractions in an isolated guinea pig ileum assay in vivo and serve as a lead compound for the development of novel drugs for the treatment of diseases caused by TMEM16A dysfunction, an inhibitor, matrine which can dramatically inhibit the growth of lung adenocarcinoma tumors in xenografted mice, and may function as an anti-lung adenocarcinoma drug targeting at TMEM16 channels
Dagmar Heinová
University of Veterinary Medicine and Pharmacy in Košice, Slovak Republic
Title: Bird and mammalian lactate dehydrogenase isoenzymes
Time : 14:30-15:00
Biography:
Dagmar Heinová has completed her PhD at the age of 30 years from the University of Veterinary Medicine in Košice, Slovak Republic. She is an Associate Professor in Biochemistry with the special focus in enzymology. She is a tutor of Clinical Biochemistry at the University and supervisor of students final thesis. In the area of lactate dehydrogenase isoenzymes studies, she published seven papers. She also developed a colorimetric method for determination of pepsin activity which was published and patented
Abstract:
Lactate dehydrogenase (EC 1.1.1.27, LDH) is an enzyme widely distributed in cells of living systems. It is involved in carbohydrate metabolism catalyzing the interconversion of lactate and pyruvate with nicotinamide adenine dinucleotide as coenzyme both in the cytoplasm as well as in mitochondria. LDH exists in several isoenzymatic forms that differs each other in their kinetic characteristics (Km, kcat), physicochemical properties (different net charge), response to the inhibition by substrate (pyruvate), and immunological response. Their different net charge predetermines their different migration rate in the electric field that is used in separating of these enzymes in research as well as in diagnostic practice. Five somatic LDH isoenzymes are detected in serum and tissues of vertebrates with heart, skeletal muscle and liver being the LDH richest organs. A buffer system of the pH values 8.6 to 8.8 is commonly used for the separation of these isoenzymes enabling to distinguish five LDH molecules in mammals. In the case of bird LDHs, the observation of all five isoforms under this pH condition is very difficult as they produce only one rather diffuse enzymatic zone. Isoelectric focusing technique in the pH range of 3 to 9 was shown to be a convenient method for bird LDH isoenzyme separation producing a good and clear resolution of all five LDH fractions in chicken (adult as well as embryonic), turkey, pheasant, and pigeon. Different pI values of LDHs of bird and mammalian origin with the similar catalytic properties probably reflect the different phylogenesis of bird and mammalian LDH molecules.
Mehmet Gokhan Habiboglu
Turkish-German University, Turkey
Title: Glycopeptides by quantum chemistry and artificial intelligence
Time : 15:00-15:30
Biography:
M. Gokhan Habiboglu has his expertise in mathematical and computational modelling of biological systems. He had interest in modelling especially the population dynamics of cell cultures and emergent structures of aromatic amino acids. Recently, he shifted his focus on deep neural networks and combined his knowledge in this area with the quantum chemistry calculations to estimate some quantum properties of carbohydrates.
Abstract:
Glycation destroys or impairs the biological function of peptides and proteins. The bacteria cell wall polymers consist of GlcNAc, which is cross-linked with oligopeptides. While glutamine is a nonessential amino acid that can be derived from glucose, some cancer cells primarily depend on glutamine for their growth, proliferation, and survival. Numerous types of cancer also depend on asparagine for cell proliferation. Thus, glucose and asparagine interactions are at the center of cancer. Moreover, Semliki Forest virus grown in mosquito cells consist of asparagine-linked oligosaccharides. Dengue virus envelope protein (E) consists of two N-linked glyscosylation sites asparagine-67 and asparagine-153. N-linked oligosaccharide side chains on flavivirus E proteins have been associated with viral morphogenesis, infectivity, and tropism. Virologically, ZIKV consists of a single-stranded, positive-sense RNA while the genome encodes three structural proteins including an E protein. Both cryo-electron microscopy and crystallization measurements supported the role of asparagine as a glycosylation site for host cell attachment. Recent studies have shown that ZIKV attacks parts of the adult brain that are central to learning and memory. Furthermore, an observable change in the brain is impaired glucose metabolism within Alzheimer´s disease progression, assessed using positron emission tomography to monitor {18F}-2-deoxy-2-fluoro-glucose uptake within the brain of Alzheimer´s disease patients. The exact molecular mechanism between O-GlcNAc and Aβ remains elusive at the atomic level. Here, we present the structures and energetics of Glc-Asn and GlcNAc-Asn complexes in an aqueous solution medium at the electronic level using quantum chemical calculations linked with artificial intelligence studies. To the best of our knowledge, this study represents the first investigations of aqueous glycopeptides usng quantum chemistry associated with artificial intelligence.
Orkid Coskuner Weber
Turkısh-German University, Turkey
Title: Quantum and statistical mechanical and bioinformatics studies in Alzheimer´s and Parkinson´s diseases
Time : 15:50-16:20
Biography:
Orkid Coskuner-Weber completed her PhD studies in biophysics and physical chemistry at the University of Cologne in Germany. She worked as a postdoctoral scientist at the Johns Hopkins University and then at Stanford University. She was a research assistant professor at George Mason University and an assistant professor at the University of Texas at San Antonio. Currently, she is an assistant professor at the Turkish-German University and took a position in Istanbul for opening the Alzheimer’s and Parkinson’s disease research center. She has been working as a scientist at the National Institute of Standards and Technology, USA, since 2005.
Abstract:
Alzheimer’s and Parkinson’s diseases affect 45 million and 10 million people worldwide. The mechanisms of these severe diseases are currently poorly understood at the atomıic and molecular levels. Intrinsically disordered proteins are at the centers of Alzheimer’s and Parkinson’s diseases. These proteins do not adopt stable structures but possess rapid conformational changes and fast aggregation processes. Thus, measurements of their chemical, physical and biological properties at the monomeric and oligomeric levels face challenges. Furthermore, oxidative stress, mitochondrial dysfunction, and genetics, as well as glucose interactions, affect the mechanism of these two neurodegenerative diseases. We study the molecular mechanisms of Alzheimer’s and Parkinson’s diseases at the atomic and molecular levels. For these purposes, we develop and apply novel quantum and statistical mechanical and bioinformatics tools. We published 30 peer-reviewed research papers and a book chapter about these topics. Here, we will discuss the usefulness of quantum and statistical mechanics and bioinformatics in the studies of complex diseases, such as Alzheimer’s and Parkinson’s diseases.
- Systems and Synthetic Biology | Pharmaceutical Biochemistry | Biochemistry and Enzymology | Computational Systems Biology | Cellular and Molecular Biology | Biophysics
Location: Colombard
Chair
Hamid Mirzaei
UT Southwestern Medical Center, USA
Co-Chair
Dagmar Heinová
University of Veterinary Medicine and Pharmacy in Košice, Slovak Republic
Session Introduction
Orkid Coskuner-Weber
Turkısh-German University, Turkey
Title: Mitochondrial dysfunction, oxidative stress and genetic factors in Alzheimer´s disease
Time : 12:00-12:30
Biography:
Orkid Coskuner-Weber is an expert in Alzheimer´s and Parkinson´s disease mechanism studies and monoclonal antibody design. She recived her Ph.D. degree from the Universitaet zu Koeln in Germany. She was a postdoc at Johns Hopkins and Stanford Universities. She was an assistant professor at George Mason University and at the University of Texas at San Antonio. She recently took a position in Istanbul for opening the Alzheimer´s and Parkinson´s disease research center. She has been associated with the National Institute of Standards and Technology since 2005. She develops and uses quantum chemical, statistical mechanical, bioinformatics, artificial intelligence and experimental tools in her research activities.
Abstract:
Alzheimer`s disease affects 10 million Americans and 44 million people worldwide. There are various biochemical mechanisms and processes that play a role in Alzheimer´s disease. These mechanisms are debated in the literature and there is currently no efficient drug that halts the progress of the disease. Efficient and effective drug design studies require detailed understanding of associated biochemical and biophysical mechanisms at the atomic level with dynamics. We investigate all biochemical processes and mechanisms associated with Alzheimer´s disease using quantum chemistry, statistical mechanics, bioinformatics, artificial intelligence and experiments. Using the information that we gain from biochemical investigations, we design monoclonal antibodies in collaboration with pharmaceutical companies. In this talk, we will present some of our studies about the roles of genetics, mitochondrial dysfunction and oxidative stress mechanisms in Alzheimer´s disease. Our theoretical and experimental results show that ATP reduces the fibrillization of disordered amyloid-β, transition metal ion coordination with amyloid-β increases the fibrillization progress and genetic factors significantly impact the fibrillization and aggregation properties of amyloid-β alloforms. Furthermore, we will provide insights into monoclonal antibody design for the treatment of Alzheimer´s disease.
Mehmet Gokhan Gokcen
Turkish-German University, Turkey Panel
Title: Impact of NAc on the glycosidic linkage flexibility of carbohydrate-peptide complexes
Time : 12:30-13:00
Biography:
Mehmet Gokhan Gokcen has completed his undergraduate, graduate and PhD degrees from Bogazici University Department of Mechanical Engineering. Since September 2017, he has been working as Assistant Professor in the Department of Mechanical Engineering at Turkish-German University. His expertise is in numerical simulation of physical systems, especially finite element analysis and computational fluid dynamics. He is currently investigating the role of glycolysis in Alzheimer's and Parkinson's disease using density functional theory and classical mechanics approaches. He is contributing to the research on the effects of genetics and on the mechanisms of oxidative stress and mitochondrial dysfunction in Alzheimer's and Parkinson's diseases.
Abstract:
A simple approach to exploring the impact of glycosylation on the conformation and biological activity of proteins is to investigate model glycopeptide species with one single monosaccharide moiety attached to amino acids. The goal originates in the experimental observation that truncation of the oligosaccharides antennae of glycoproteins does not yield dramatic conformational and immunological changes, as opposed to the removal of the first glycan moiety. In the course of evolution, prokaryotic organisms developed a considerable diversity in the supramolecular architecture of their multi-layered cell boundaries. One of the most commonly observed bacterial cell surface structures is two-dimensional arrays of proteinaceous subunits termed S-layers. They represent almost universal features on archaebacteria cell envelopes and were already detected in hundreds of different species of nearly every taxonomic group of walled eubacteria. S-layer like structures have also been observed in bacterial sheaths and on the surface of cell wall eukaryotic algae. Since S-layers are found in Gram-positive and Gram-negative eubacteria and archaebacteria they can be associated with quite a different cell envelope structures such as peptidoglycans (glucose-serine complexes). In fact, chemical analyses and genetic studies of S-layers of a variety of eubacteria revealed that composed of a protein or glycoprotein species. The glycosidic linkage flexibilities of glucopyranose-serine species in aqueous solution are difficult to investigate using conventional tools due to their high flexibility and solvent effects. Quantum chemical techniques provide a solution for these studies. We present here the structural and energetic properties of glucose-serine complexes in water and the impact of NAc on the structural and energetic properties of glucose-serine using first-principles calculations.
Oladepo Mutiu Lolade
Adekunle Ajasin University, Nigeria
Title: Effect of saponin from Solanum anguivi on heart function of Alloxan induced Diabetic rats
Time : 14:00-14:30
Biography:
Oladepo Mutiu Lolade is currently studying for his Master’s degree at Department of Biochemistry, Adekunle Ajasin University, where he bagged his Bachelor’s degree. He is a fully baked, technically inclined, scientifically unbiased and self-motivated researcher with a good laboratory proficiency. He is presently a Scientific Officer at General Hospital Akure Ondo State, Nigeria. He is a competent and enthusiastic researcher with interest in Nutrition and Cardiovascular Diseases. His keen interest understanding the contribution of African diet and nutrition to cardiovascular health has driven him into various research that make use of experimental animal models to investigate the effects of commonly consumed Nigerian foods on markers of cardiovascular health
Abstract:
Solanum anguivi is a semi-domestic indigenous vegetable very valuable in many African countries with potential to become a cultivated market vegetable in Nigeria. Uptake of Solanum anguivi cause hypoglycemic effect, hypertension etc. The effect of Saponin from Solanum anguivi on heart function of the alloxan-induced diabetic rat was investigated in this study. Twenty four (24) rats of average weight 120g were randomly divided into six (6) groups A-F. Group A (control) rats were given 2.0ml of distilled water, Group B (Diabetic control), Group C to F were diabetic rats which were administered 20mg/kg, 40mg/kg and 80mg/kg Saponin from Solanum anguivi respectively for 14 days. The results showed that there was a significant reduction in plasma glucose in the diabetic rat to almost the level in the control. The result also shows that there were a significant reduction in Aspartate Aminotransferase (AST) and Alanine aminotransferase (ALT) activities in serum and heart compared with the control (p<0.05). This study shows that Solanum anguivi fruit has an anti-diabetic effect on alloxan induced diabetic rat.
Harun Pirim
King Fahd University of Petroleum and Minerals, Saudi Arabia
Title: Descriptive and predictive analysis of gene co-expression networks
Time : 14:30-15:00
Biography:
Harun Pirim received his PhD degree in Industrial and Systems Engineering (ISE) from Mississippi State University in May 2011. Harun worked on microarray data analysis in collaboration with Computer Science and Forestry departments. His research interests include mathematical programming and heuristic applications in biology, sociology, and supply chain fields focusing mainly on graph mining. He has several papers published in Computers and Operations Research, Computers in Biology and Medicine, conference proceedings, book chapters and a brief Springer book on supply chain optimization.
Abstract:
Ample availability of gene co-expression data challenges researchers to find and apply unique approaches for extracting biological information to infer about gene functions or predict gene-disease relations. By means of reliable co-expression network construction techniques compiled networks exist and they require further predictive analysis to focus on the genes or groups of the genes exhibiting certain patterns reflected on the co-expression networks. We propose an integrated network analysis where social network descriptive analysis techniques are borrowed to summarize some structural features of the network. Then, the features are employed in optimization models to find groups of genes exhibiting certain patterns