Abstract
Homology modeling has become an essential tool for studying proteins that are targets for medical drug design.This paper describes the approach we developed that combines sequence decomposition techniques with distance geometry algorithms for homology modeling to determine functionally important regions of proteins.We show here the application of these techniques to targets of medical interest chosen from those included in the CASP5 (Critical Assessment of Techniques for Protein Structure Prediction)competition,including the dihydroneopterin aldolase from Mycobacterium tuberculosis ,RNase III of Thermobacteria maritima ,and the NO-transporter nitrophorin from saliva of the bedbug Cimex lectularius .Physical chemical property (PCP)motifs,identified in aligned sequences with our MASIA program,can be used to select among different alignments returned by fold recognition servers.They can also be used to suggest functions for hypothetical proteins,as we illustrate for target T188.Once a suitable alignment has been made with the template,our modeling suite MPACK generates a series of possible models. The models can then be selected according to their match in areas known to be conserved in protein families. Alignments based on motifs can improve the structural matching of residues in the active site.The quality of the local structure of our 3D models near active sites or epitopes makes them useful aids for drug and vaccine design.Further,the PCP motif approach,when combined with a structural filter,can be a potent way to detect areas involved in activity and to suggest function for novel genome sequences.
Keywords: casp5, masia, pcpmer, sequence motifs, physical-chemical properties, bayesian statistics, functional annotation, drug, vaccine design
Current Medicinal Chemistry
Title: Using Property Based Sequence Motifs and 3D Modeling to Determine Structure and Functional Regions of Proteins
Volume: 11 Issue: 5
Author(s): Ovidiu Ivanciuc, Numan Oezguen, Venkatarajan S. Mathura, Catherine H. Schein, Yuan Xu and Werner Braun
Affiliation:
Keywords: casp5, masia, pcpmer, sequence motifs, physical-chemical properties, bayesian statistics, functional annotation, drug, vaccine design
Abstract: Homology modeling has become an essential tool for studying proteins that are targets for medical drug design.This paper describes the approach we developed that combines sequence decomposition techniques with distance geometry algorithms for homology modeling to determine functionally important regions of proteins.We show here the application of these techniques to targets of medical interest chosen from those included in the CASP5 (Critical Assessment of Techniques for Protein Structure Prediction)competition,including the dihydroneopterin aldolase from Mycobacterium tuberculosis ,RNase III of Thermobacteria maritima ,and the NO-transporter nitrophorin from saliva of the bedbug Cimex lectularius .Physical chemical property (PCP)motifs,identified in aligned sequences with our MASIA program,can be used to select among different alignments returned by fold recognition servers.They can also be used to suggest functions for hypothetical proteins,as we illustrate for target T188.Once a suitable alignment has been made with the template,our modeling suite MPACK generates a series of possible models. The models can then be selected according to their match in areas known to be conserved in protein families. Alignments based on motifs can improve the structural matching of residues in the active site.The quality of the local structure of our 3D models near active sites or epitopes makes them useful aids for drug and vaccine design.Further,the PCP motif approach,when combined with a structural filter,can be a potent way to detect areas involved in activity and to suggest function for novel genome sequences.
Export Options
About this article
Cite this article as:
Ivanciuc Ovidiu, Oezguen Numan, Mathura S. Venkatarajan, Schein H. Catherine, Xu Yuan and Braun Werner, Using Property Based Sequence Motifs and 3D Modeling to Determine Structure and Functional Regions of Proteins, Current Medicinal Chemistry 2004; 11 (5) . https://dx.doi.org/10.2174/0929867043455819
DOI https://dx.doi.org/10.2174/0929867043455819 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Monocyte and Macrophage Dysfunction as a Cause of HIV-1 Induced Dysfunction of Innate Immunity
Current Molecular Medicine Advances in Zebrafish High Content and High Throughput Technologies
Combinatorial Chemistry & High Throughput Screening Macrophage Targeted Cellular Carriers for Effective Delivery of Anti-Tubercular Drugs
Recent Patents on Anti-Infective Drug Discovery Bis(2-aminoimidazolines) and Bisguanidines: Synthetic Approaches, Antiparasitic Activity and DNA Binding Properties
Current Medicinal Chemistry Is tRNA Binding or tRNA Mimicry Mandatory for Translation Factors?
Current Protein & Peptide Science Skeletal Muscle in Cancer Cachexia: The Ideal Target of Drug Therapy
Current Cancer Drug Targets Synthesis and In Vitro Antibacterial Screening of some New 2,4,6-Trisubstituted-1,3,5-Triazine Derivatives
Letters in Drug Design & Discovery Targeting the Mannose Receptor with Mannosylated Subunit Vaccines
Current Medicinal Chemistry QSAR, Docking, and CoMFA Studies of GSK3 Inhibitors
Current Pharmaceutical Design Specific Biologic Therapy with Tumor Necrosis Factor Inhibitors in Patients with Inflammatory Myopathy
Current Rheumatology Reviews Editorial [ Infectious Disorders Drug Targets - An Arsenal of Knowledge on Pathogen Targets ]
Infectious Disorders - Drug Targets Carbohydrate Mimics and Lectins: A Source of New Drugs and Therapeutic Opportunities
Mini-Reviews in Medicinal Chemistry Recent Advances for Cell / Gene Therapy in Rheumatoid Arthritis
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Lacticin 3147 - Biosynthesis, Molecular Analysis, Immunity, Bioengineering and Applications
Current Protein & Peptide Science The Role of Drug Transporters in the Pharmacokinetics of Antibiotics
Current Drug Metabolism Solubilization and Antitumor Activity of Oleanolic Acid Lysinate
Current Analytical Chemistry SAR, QSAR and Docking of Anticancer Flavonoids and Variants: A Review
Current Topics in Medicinal Chemistry Lessons from Seven Decades of Antituberculosis Drug Discovery
Current Topics in Medicinal Chemistry Synthesis, Biological Evaluation and Molecular Docking Studies of New Pyrazolines as an Antitubercular and Cytotoxic Agents
Infectious Disorders - Drug Targets Surface Energy Determined by Inverse Gas Chromatography as a Tool to Investigate Particulate Interactions in Dry Powder Inhalers
Current Pharmaceutical Design