Download or read book Automated Structural Annotation of the Malaria Proteome and Identification of Candidate Proteins for Modelling and Crystallization Studies written by Yolandi Joubert and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is the cause of over one million deaths per year, primarily in African children. The parasite responsible for the most virulent form of malaria, is Plasmodium falciparum. Protein structure plays a pivotal role in elucidating mechanisms of parasite functioning and resistance to anti-malarial drugs. Protein structure furthermore aids the determination of protein function, which can together with the structure be used to identify novel drug targets in the parasite. However, various structural features in P. falciparum proteins complicate the experimental determination of protein three dimensional structures. Furthermore, the presence of parasite-specific inserts results in reduced similarity of these proteins to orthologous proteins with experimentally determined structures. The lack of solved structures in the malaria parasite, together with limited similarities to proteins in the Protein Data Bank, necessitate genome-scale structural annotation of P. falciparum proteins. Additionally, the annotation of a range of structural features facilitates the identification of suitable targets for structural studies. An integrated structural annotation system was constructed and applied to all the predicted proteins in P. falciparum, Plasmodium vivax and Plasmodium yoelii. Similarity searches against the PDB, Pfam, Superfamily, PROSITE and PRINTS were included. In addition, the following predictions were made for the P. falciparum proteins: secondary structure, transmembrane helices, protein disorder, low complexity, coiled-coils and small molecule interactions. P. falciparum protein-protein interactions and proteins exported to the RBC were annotated from literature. Finally, a selection of proteins were threaded through a library of SCOP folds. All the results are stored in a relational PostgreSQL database and can be viewed through a web interface (http://deepthought.bi.up.ac.za:8080/Annotation). In order to select groups of proteins which fulfill certain criteria with regard to structural and functional features, a query tool was constructed. Using this tool, criteria regarding the presence or absence of all the predicted features can be specified. Analysis of the results obtained revealed that P. falciparum protein-interacting proteins contain a higher percentage of predicted disordered residues than non-interacting proteins. Proteins interacting with 10 or more proteins have a disordered content concentrated in the range of 60-100%, while the disorder distribution for proteins having only one interacting partner, was more evenly spread. Comparisons of structural and sequence features between the three species, revealed that P. falciparum proteins tend to be longer and vary more in length than the other two species. P. falciparum proteins also contained more predicted low complexity and disorder content than proteins from P. yoelii and P. vivax. P. falciparumprotein targets for experimental structure determination, comparative modeling and in silico docking studies were putatively identified based on structural features. For experimental structure determination, 178 targets were identi_ed. These targets contain limited contents of predicted transmembrane helix, disorder, coiled-coils, low complexity and signal peptide, as these features may complicate steps in the experimental structure determination procedure. In addition, the targets display low similarity to proteins in the PDB. Comparisons of the targets to proteins with crystal structures, revealed that the structures and predicted targets had similar sequence properties and predicted structural features. A group of 373 proteins which displayed high levels of similarity to proteins in the PDB, were identified as targets for comparitive modeling studies. Finally, 197 targets for in silico docking were identified based on predicted small molecule interactions and the availability of a 3D structure.

Download or read book CryoEM Enabled Approaches to Structure Determination of Endogenous Protein Complexes Implicated in the Pathogenesis of the Malaria Parasite Plasmodium Falciparum written by Chi-Min Ho and published by . This book was released on 2019 with total page 151 pages. Available in PDF, EPUB and Kindle. Book excerpt: The complexity and breadth of the host-cell remodeling machinery in the malaria parasite P. falciparum make it a rich and exciting system for the study of host-pathogen interfaces, particularly as many of the molecular mechanisms underlying this parasite's ability to hijack human red blood cells remain unclear. Furthermore, the P. falciparum proteome has proven recalcitrant to structural and biochemical characterization using recombinant methods, making it an intriguing model system for the development of new methods that leverage recent advances in cryoEM to enable structural studies of previously intractable systems at near-atomic resolution. The work presented here makes significant contributions in both these regards. First, we use a targeted, CRISPR-enabled "top down" approach to determine near-atomic resolution structures of the unique malaria parasite translocon PTEX, which we purified directly from P. falciparum parasites in multiple functional states, yielding the first near-atomic resolution cryoEM structures of a protein isolated directly from an endogenous source using an epitope tag inserted into the endogenous locus with CRISPR-Cas9 gene editing. We then developed a "bottom up" endogenous structural proteomics method whereby protein complexes enriched directly from the cellular milieu are identified by imaging and structure determination using cryoEM and mass spectrometry. As a proof of principle, we successfully used this approach to obtain near-atomic resolution structures of multiple protein complexes from the P. falciparum proteome, which has previously proven recalcitrant to expression in recombinant systems, precluding structure determination by X-ray crystallography or NMR. The body of work described here addresses a known need for methods that overcome the limitations of structural biology approaches that depend on recombinant systems, opening the door for high resolution structure determination of a vast number of previously intractable biological systems.

Download or read book Structural Studies of Malaria Proteins written by Christina Mayer and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is a disease of global importance, causing hundreds of thousand of deaths a year. The majority or deaths are caused by Plasmodium falciparum, a parasite transmitted by the mosquito Anopheles. Its pathogenicity largely results from an ability to transform infected erythrocytes by creating knob-like structures that result in endothelial adhesion. Two major components of these knob structures have been identified as P. falciparum erythrocyte membrane protein 1 (PjEMPI) and knob-associated histidine rich protein (KAHRP). The extracellular fragment of PjEMPI is responsible for antigenic variability and cytoadherence while its intracellular domain (ATS) connects to the cytoskeleton via interactions with other plasmodium-encoded proteins. In addition, perforin-like proteins (PLPs) with a MACPF domain have been identified in the genome of Plasmodium. PLPs are highly conserved and are expressed in various life-cycle stages of the parasite. They are believed to form pores in membranes of the host cell but their structure is yet unknown. The aim of the work in this thesis was to obtain new information about the structure and role of malaria proteins, thus giving a better understanding of the disease and its possible treatment. Studies of numerous designed constructs of the ATS family were carried out using biophysical methods including high resolution NMR, SAXS and CD. These revealed that ATS domains are mainly unstructured with a relatively small folded core, consisting of a bundle of a-helices. Surprisingly, no evidence could be found for ATS binding to KAHRP in solution conditions although previous pull-down data had indicated an interaction. Bioinformatics analysis and yeast-two-hybrid data suggested, however, that there is a conserved protein interaction epitope on the central flexible part of ATS. It was shown, using fluorescence anisotropy measurements that this part of ATS associates with a parasite protein containing a PHIST (Plasmodium helical interspersed sub-telomeric) domain. Expression constructs of the PLP protein family were designed and manufactured, with the aim of enabling structural studies of these putative pore proteins.

Download or read book Heat Shock Proteins of Malaria written by Addmore Shonhai and published by Springer. This book was released on 2022-09-28 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This new edition describes the role of heat shock proteins in the life cycle of malaria parasites, particularly in the context of intracellular parasite stages. Thoroughly revised, this work provides a general introduction to the structural and functional features of heat shock proteins with a special focus on their role as molecular chaperones in ensuring protein quality control. The emphasis is on the heat shock protein families from Plasmodium falciparum, and their role in proteostasis and the development of malaria pathology. Moreover, the authors explore the latest prospects of targeting heat shock proteins in antimalarial drug discovery either directly or in combination therapies. Readers will experience a functional analysis of the individual families of heat shock proteins and their cooperation in functional networks, including both the parasite-resident proteome and the exportome released into host cells during intracellular stages. Subcellular and extracellular organelles such as the apicoplast and the Maurer’s Clefts associated with Plasmodium species are discussed in detail. The book highlights the role of heat shock proteins in the development and function of these structures. Biochemical expertise and the inclusion of novel therapeutic solutions make this collection a unique reference for experts in heat shock protein research, parasitology and infectious diseases, cell stress, molecular biology and drug discovery. Not least, advances in malaria control will contribute to ending epidemics and ensuring healthy lives in line with the UN Sustainable Development Goals.

Download or read book Feasibility Optimisation and Scale up Studies for the Production of P Falciparum Putative Vaccine Candidates for a Malaria Microarray based Antigenicity Screening written by Giorgio Mazzoleni and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Computational Support Systems for Prediction and Characterization of Protein Crystallization Outcomes written by Marcin Jerzy Mizianty and published by . This book was released on 2013 with total page 124 pages. Available in PDF, EPUB and Kindle. Book excerpt: Analysis of protein structures may reveal their function, regulation and interactions. Almost 90% of the known protein structures were solved using X-ray crystallography; however, many more structures remain unsolved. Protein Structure Initiative (PSI) project was created to speed up structure determination. PSI includes structural genomics (SG) centers that perform high-throughput crystallization which processes hundreds of proteins using standardized protocols. Large quantities of crystallization data generated by PSI fueled research that looked into proteins' properties associated with success of crystallization. In spite of intense research crystallization of proteins is still among the most complex and least understood problems in structural biology. Since SG centers do not focus on individual proteins, but rather on covering the protein structure space, they have certain flexibility in selection of targets. At the beginning of my PhD program we designed and assessed three accurate methods that predict crystallization propensity based on a protein sequence. These methods could be used to prioritize targets based on their predicted propensity for the successful structure determination. We observed that as the crystallization protocols are updated the predictors of crystallization propensity need to be correspondingly upgraded and enhanced. To this end, in the course of the thesis we developed an accurate predictor that generates crystallization propensity and indicates causes of the potential crystallization failure, which can occur at any of the three major steps in the protein crystallization protocol: production of protein material, purification, and production of crystals. Our predictors are empirically compared against state-of-the-art in the field demonstrating favorable predictive performance. Finally, we designed another accurate and runtime-efficient method which we then used to perform first-of-its-kind large-scale analysis of crystallization propensity for proteins encoded in 1,953 fully sequenced genomes. Analysis of these predictions shows that current X-ray crystallography combined with homology modeling could provide an average per-proteome structural coverage of 73% with over 60% coverage for archaea and bacterial proteomes, and between 35 and 70% for eukaryotes. Moreover, our study revealed that use of knowledge-based target selection increases coverage by a significant margin, which for majority of organisms is between 25 to 40%.

Download or read book Artificial Intelligence in Drug Discovery written by Nathan Brown and published by Royal Society of Chemistry. This book was released on 2020-11-04 with total page 425 pages. Available in PDF, EPUB and Kindle. Book excerpt: Following significant advances in deep learning and related areas interest in artificial intelligence (AI) has rapidly grown. In particular, the application of AI in drug discovery provides an opportunity to tackle challenges that previously have been difficult to solve, such as predicting properties, designing molecules and optimising synthetic routes. Artificial Intelligence in Drug Discovery aims to introduce the reader to AI and machine learning tools and techniques, and to outline specific challenges including designing new molecular structures, synthesis planning and simulation. Providing a wealth of information from leading experts in the field this book is ideal for students, postgraduates and established researchers in both industry and academia.

Download or read book Encyclopedia of Malaria written by and published by Springer. This book was released on 2018-07-12 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Encyclopedia of Malaria represents a vast databank of information about the study of malaria. It provides an overview of the historical, rapid and significant developments that have occurred in malaria research, including the 2002 genome sequencing of Plasmodium falciparum and its mosquito vector, Anopheles gambiae. This work provides a concise source of up-to-date research findings in the form of definitions and essays and present comprehensive coverage of topics from history to findings to diagnosis and treatment, written by recognized malaria researchers with practical experience. It appeals to a diverse audience, including malaria researchers, teachers, investigators and public health professionals.

Download or read book Homology Molecular Modeling written by Rafael Trindade Maia and published by BoD – Books on Demand. This book was released on 2021-03-10 with total page 147 pages. Available in PDF, EPUB and Kindle. Book excerpt: Homology modeling is an extremely useful and versatile technique that is gaining more and more space and demand in research in computational and theoretical biology. This book, “Homology Molecular Modeling - Perspectives and Applications”, brings together unpublished chapters on this technique. In this book, 7 chapters are intimately related to the theme of molecular modeling, carefully selected and edited for academic and scientific readers. It is an indispensable read for anyone interested in the areas of bioinformatics and computational biology. Divided into 4 sections, the reader will have a didactic and comprehensive view of the theme, with updated and relevant concepts on the subject. This book was organized from researchers to researchers with the aim of spreading the fascinating area of molecular modeling by homology.

Download or read book Innovations and Implementations of Computer Aided Drug Discovery Strategies in Rational Drug Design written by Sanjeev Kumar Singh and published by Springer Nature. This book was released on 2021-02-02 with total page 334 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents various computer-aided drug discovery methods for the design and development of ligand and structure-based drug molecules. A wide variety of computational approaches are now being used in various stages of drug discovery and development, as well as in clinical studies. Yet, despite the rapid advances in computer software and hardware, combined with the exponential growth in the available biological information, there are many challenges that still need to be addressed, as this book shows. In turn, it shares valuable insights into receptor-ligand interactions in connection with various biological functions and human diseases. The book discusses a wide range of phylogenetic methods and highlights the applications of Molecular Dynamics Simulation in the drug discovery process. It also explores the application of quantum mechanics in order to provide better accuracy when calculating protein-ligand binding interactions and predicting binding affinities. In closing, the book provides illustrative descriptions of major challenges associated with computer-aided drug discovery for the development of therapeutic drugs. Given its scope, it offers a valuable asset for life sciences researchers, medicinal chemists and bioinformaticians looking for the latest information on computer-aided methodologies for drug development, together with their applications in drug discovery.

Download or read book RNA Spectroscopy written by Véronique Arluison and published by Humana. This book was released on 2020-02-01 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume looks at the different spectroscopic and biophysical methods used by researchers to study the structure and folding of RNA, and to follow their interactions with proteins. The chapters in this book cover topics such as single-molecule spectroscopy of multiple RNA species; surface plasmon resonance, MS or microcalorimetry for investigating molecular interactions with RNA; FTIR, SAXS, SANS and SRCD spectroscopies to analyze RNA structure; use of fluorescent nucleotides to map RNA-binding sites on proteins surfaces or CryoEM; and much more. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and comprehensive, RNA Spectroscopy: Methods and Protocols is a valuable resource for anyone interested in learning more about this developing field.

Download or read book Converging Technologies for Improving Human Performance written by Mihail C. Roco and published by Springer Science & Business Media. This book was released on 2013-04-17 with total page 477 pages. Available in PDF, EPUB and Kindle. Book excerpt: M. C. Roco and W.S. Bainbridge In the early decades of the 21st century, concentrated efforts can unify science based on the unity of nature, thereby advancing the combination of nanotechnology, biotechnology, information technology, and new technologies based in cognitive science. With proper attention to ethical issues and societal needs, converging in human abilities, societal technologies could achieve a tremendous improvement outcomes, the nation's productivity, and the quality of life. This is a broad, cross cutting, emerging and timely opportunity of interest to individuals, society and humanity in the long term. The phrase "convergent technologies" refers to the synergistic combination of four major "NBIC" (nano-bio-info-cogno) provinces of science and technology, each of which is currently progressing at a rapid rate: (a) nanoscience and nanotechnology; (b) biotechnology and biomedicine, including genetic engineering; (c) information technology, including advanced computing and communications; (d) cognitive science, including cognitive neuroscience. Timely and Broad Opportunity. Convergence of diverse technologies is based on material unity at the nanoscale and on technology integration from that scale.

Download or read book Epitope Mapping Protocols written by Johan Rockberg and published by Humana. This book was released on 2019-05-15 with total page 284 pages. Available in PDF, EPUB and Kindle. Book excerpt: This third edition volume expands on the previous editions with more detailed research on the characterization of antibody antigen interactions between different users with different requirements. The chapters in this book are divided into four parts: Part One looks at the entire native antigen and covers traditional structural biology techniques such as nuclear magnetic resonance and x-ray crystallography. Part Two talks about protein fragments derived from antigens, and discusses binding regions within antigen sequence using bacterial surface display and ELISA, for example. Part Three describes the use of surface plasmon resonance spectroscopy and biolayer interferometry, and Part Four highlights methods used to identify new antigens and assess antibody cross-reactivity. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Thorough and cutting-edge, Epitope Mapping Protocols, Third Edition is a valuable resource for anyone interested in furthering their research in this expanding field.

Download or read book Introduction to Bioinformatics written by Arthur Lesk and published by . This book was released on 2019-05 with total page 433 pages. Available in PDF, EPUB and Kindle. Book excerpt: The ideal text for biology students encountering bioinformatics for the first time, Introduction to Bioinformatics describes how recent technological advances in the field can be used as a powerful set of tools for receiving and analyzing biological data.

Download or read book Industrial Pharmaceutical Biotechnology written by Heinrich Klefenz and published by Wiley-VCH. This book was released on 2002-04-22 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume focuses on pharmaceutical biotechnology as a key area of life sciences. The complete range of concepts, processes and technologies of biotechnology is applied in modern industrial pharmaceutical research, development and production. The results of genome sequencing and studies of biological-genetic function are combined with chemical, micro-electronic and microsystem technology to produce medical devices and diagnostic biochips. A multitude of biologically active molecules is expanded by additional novel structures created with newly arranged gene clusters and bio-catalytic chemical processes. New organisational structures in the co-operation of institutes, companies and networks enable faster knowledge and product development and immediate application of the results of research and process development. This book is the ideal source of information for scientists and engineers in research and development, for decision-makers in biotech, pharma and chemical corporations, as well as for research institutes, but also for founders of biotech companies and people working for venture capital corporations.

Download or read book Proteomics for Biological Discovery written by Timothy D. Veenstra and published by John Wiley & Sons. This book was released on 2006-06-12 with total page 361 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written by recognized experts in the study of proteins, Proteomics for Biological Discovery begins by discussing the emergence of proteomics from genome sequencing projects and a summary of potential answers to be gained from proteome-level research. The tools of proteomics, from conventional to novel techniques, are then dealt with in terms of underlying concepts, limitations and future directions. An invaluable source of information, this title also provides a thorough overview of the current developments in post-translational modification studies, structural proteomics, biochemical proteomics, microfabrication, applied proteomics, and bioinformatics relevant to proteomics. Presents a comprehensive and coherent review of the major issues faced in terms of technology development, bioinformatics, strategic approaches, and applications Chapters offer a rigorous overview with summary of limitations, emerging approaches, questions, and realistic future industry and basic science applications Discusses higher level integrative aspects, including technical challenges and applications for drug discovery Accessible to the novice while providing experienced investigators essential information Proteomics for Biological Discovery is an essential resource for students, postdoctoral fellows, and researchers across all fields of biomedical research, including biochemistry, protein chemistry, molecular genetics, cell/developmental biology, and bioinformatics.

Download or read book Complex System Modelling and Control Through Intelligent Soft Computations written by Quanmin Zhu and published by Springer. This book was released on 2014-11-29 with total page 856 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book offers a snapshot of the theories and applications of soft computing in the area of complex systems modeling and control. It presents the most important findings discussed during the 5th International Conference on Modelling, Identification and Control, held in Cairo, from August 31-September 2, 2013. The book consists of twenty-nine selected contributions, which have been thoroughly reviewed and extended before their inclusion in the volume. The different chapters, written by active researchers in the field, report on both current theories and important applications of soft-computing. Besides providing the readers with soft-computing fundamentals, and soft-computing based inductive methodologies/algorithms, the book also discusses key industrial soft-computing applications, as well as multidisciplinary solutions developed for a variety of purposes, like windup control, waste management, security issues, biomedical applications and many others. It is a perfect reference guide for graduate students, researchers and practitioners in the area of soft computing, systems modeling and control.