Abstract
Integrated bioinformatic approaches to drug discovery exploit computational techniques to examine the flow of information from genome to structure to function. Informatics is being be used to accelerate and rationalize the process of antimycobacterial drug discovery and design, with the immediate goals to identify viable drug targets and produce a set of critically evaluated protein target models and corresponding set of probable lead compounds. Bioinformatic approaches are being successfully used for selection and prioritization of putative mycobacterial drug target genes; computational modelling and x-ray structure validation of protein targets with drug lead compounds; simulated docking and virtual screening of potential lead compounds; and lead validation and optimization using structure-activity and structurefunction relationships. Active sites can be identified, characterizing patterns of conserved residues and, where relevant, predicting catalytic residues, thus providing information to aid the design of selective and efficacious pharmacophores. In this review, we describe selected recent progress in antimycobacterial drug design, illustrating the strengths and limitations of current structural bioinformatic approaches as tools in the fight against tuberculosis.
Keywords: tuberculosis, structural bioinformatics, mycobacteria, virtual screening, structure-based drug design
Current Pharmaceutical Design
Title: Structural Bioinformatic Approaches to the Discovery of New Antimycobacterial Drugs
Volume: 10 Issue: 26
Author(s): Katherine Kantardjieff and Bernhard Rupp
Affiliation:
Keywords: tuberculosis, structural bioinformatics, mycobacteria, virtual screening, structure-based drug design
Abstract: Integrated bioinformatic approaches to drug discovery exploit computational techniques to examine the flow of information from genome to structure to function. Informatics is being be used to accelerate and rationalize the process of antimycobacterial drug discovery and design, with the immediate goals to identify viable drug targets and produce a set of critically evaluated protein target models and corresponding set of probable lead compounds. Bioinformatic approaches are being successfully used for selection and prioritization of putative mycobacterial drug target genes; computational modelling and x-ray structure validation of protein targets with drug lead compounds; simulated docking and virtual screening of potential lead compounds; and lead validation and optimization using structure-activity and structurefunction relationships. Active sites can be identified, characterizing patterns of conserved residues and, where relevant, predicting catalytic residues, thus providing information to aid the design of selective and efficacious pharmacophores. In this review, we describe selected recent progress in antimycobacterial drug design, illustrating the strengths and limitations of current structural bioinformatic approaches as tools in the fight against tuberculosis.
Export Options
About this article
Cite this article as:
Kantardjieff Katherine and Rupp Bernhard, Structural Bioinformatic Approaches to the Discovery of New Antimycobacterial Drugs, Current Pharmaceutical Design 2004; 10 (26) . https://dx.doi.org/10.2174/1381612043383205
DOI https://dx.doi.org/10.2174/1381612043383205 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employ in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, prediction, to monitor of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal fluid ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...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
-
Tuberculosis: Current Treatment, Diagnostics, and Newer Antitubercular Agents in Clinical Trials
Infectious Disorders - Drug Targets Recent Advances in Design of Potential Quinoxaline Anti-Infectives
Current Medicinal Chemistry Autoimmune Diseases in Gastroenterology
Current Pharmaceutical Design Drug Discovery and Protein Tyrosine Phosphatases
Current Medicinal Chemistry Utility of Non-Conventional Applications of Anti-VEGF Treatment in Selected Retinal Diseases
Current Drug Therapy Recent Applications of Birch Reduction in Total Synthesis of Natural Products
Current Organic Chemistry Salmonella as Live Trojan Horse for Vaccine Development and Cancer Gene Therapy
Current Gene Therapy Sterol Biosynthesis Pathway as an Alternative for the Anti-Protozoan Parasite Chemotherapy
Current Medicinal Chemistry Detection of Non-Tuberculosis Mycobacteria by Real Time PCR
Anti-Infective Agents Integrating the Universe of Effector and Regulatory Immune Cell Subsets: An Emerging Role of Protein-Glycan Interactions
Current Immunology Reviews (Discontinued) Antiidiotype-Derived Killer Peptides As New Potential Tools to Combat HIV-1 and AIDS-Related Opportunistic Pathogens
Anti-Infective Agents in Medicinal Chemistry Anti-Inflammatory Drugs in Psychiatry
Inflammation & Allergy - Drug Targets (Discontinued) 1-R-2-([1,2,4]Triazolo[1,5-c]quinazoline-2-ylthio)etanon(ol)s: Synthesis, Bioluminescence Inhibition, Molecular Docking Studies, Antibacterial and Antifungal Activities
Current Computer-Aided Drug Design Mini Heme-Proteins: Designability of Structure and Diversity of Functions
Current Protein & Peptide Science Current Therapeutic Approaches in Inflammatory Bowel Disease
Current Pharmaceutical Design Patent Selections:
Recent Patents on Anti-Infective Drug Discovery Biologic Therapy in Inflammatory and Immunomediated Skin Diseases: Safety Profile
Current Drug Safety Significance of Lipolytic Enzymes in Pathogenesis and Treatment of Neglected Diseases
Current Protein & Peptide Science DNA-Minor Groove Binding Agents as Anti-Tubercular Probes. Old Tools for a New Challenge?
Anti-Infective Agents Immunomodulatory Properties of Antibiotics
Current Molecular Pharmacology