Abstract
Malaria remains one of the most burdensome human infectious diseases, with a high rate of resistance outbreaks and a constant need for the discovery of novel antimalarials and drug targets. For several reasons, Plasmodial proteins are difficult to characterise structurally using traditional physical approaches. However, these problems can be partially overcome using a number of in silico approaches. This review describes the peculiarities of malaria proteins and then details various in silico strategies to select and allow descriptions of the molecular structures of drug target candidates as well as subsequent rational approaches for drug design. Chiefly, homology modelling with specific focus on unique aspects of malaria proteins including low homology, large protein size and the presence of parasite-specific inserts is addressed and alternative strategies including multiple sequence and structure-based prediction methods, samplingbased approaches that aim to reveal likely global or shared features of a Plasmodial structure and the value of molecular dynamics understanding of unique features of Plasmodial proteins are discussed. Once a detailed description of the drug target is available, in silico approaches to the specific design of an inhibitory drug thereof becomes invaluable as an economic and rational alternative to chemical library screening.
Keywords: Malaria, antimalarials, pharmacophore, structure-based drug discovery, in silico
Infectious Disorders - Drug Targets
Title: Antimalarial Drug Discovery: In Silico Structural Biology and Rational Drug Design
Volume: 9 Issue: 3
Author(s): TAP de Beer, GA Wells, PB Burger, F. Joubert, E. Marechal, L. Birkholtz and AI Louw
Affiliation:
Keywords: Malaria, antimalarials, pharmacophore, structure-based drug discovery, in silico
Abstract: Malaria remains one of the most burdensome human infectious diseases, with a high rate of resistance outbreaks and a constant need for the discovery of novel antimalarials and drug targets. For several reasons, Plasmodial proteins are difficult to characterise structurally using traditional physical approaches. However, these problems can be partially overcome using a number of in silico approaches. This review describes the peculiarities of malaria proteins and then details various in silico strategies to select and allow descriptions of the molecular structures of drug target candidates as well as subsequent rational approaches for drug design. Chiefly, homology modelling with specific focus on unique aspects of malaria proteins including low homology, large protein size and the presence of parasite-specific inserts is addressed and alternative strategies including multiple sequence and structure-based prediction methods, samplingbased approaches that aim to reveal likely global or shared features of a Plasmodial structure and the value of molecular dynamics understanding of unique features of Plasmodial proteins are discussed. Once a detailed description of the drug target is available, in silico approaches to the specific design of an inhibitory drug thereof becomes invaluable as an economic and rational alternative to chemical library screening.
Export Options
About this article
Cite this article as:
de Beer TAP, Wells GA, Burger PB, Joubert F., Marechal E., Birkholtz L. and Louw AI, Antimalarial Drug Discovery: In Silico Structural Biology and Rational Drug Design, Infectious Disorders - Drug Targets 2009; 9 (3) . https://dx.doi.org/10.2174/1871526510909030304
DOI https://dx.doi.org/10.2174/1871526510909030304 |
Print ISSN 1871-5265 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3989 |
- 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
-
Neutropenia in Preterm Infants
Current Pediatric Reviews Synthesis of Some Novel 4-(Arylideneamino)-N'-((2-chloro-8-methylquinolin- 3-yl)methylene)-3-phenyl-2-thioxo-2,3-dihydrothiazole-5-carbohydrazides as Potential Antimicrobial Agents
Letters in Drug Design & Discovery Cancer Drug Discovery Targeting Histone Methyltransferases: An Update
Current Medicinal Chemistry Searching for Potential HDAC2 Inhibitors: Structure-activity Relationship Studies on Indole-based Hydroxamic Acids as an Anticancer Agent
Letters in Drug Design & Discovery Alzheimer's Disease: Related Targets, Synthesis of Available Drugs, Bioactive Compounds Under Development and Promising Results Obtained from Multi-target Approaches
Current Drug Targets Cerebral Malaria - A Neurovascular Pathology with Many Riddles Still to be Solved
Current Neurovascular Research Substituted 3-R-2,8-Dioxo-7,8-dihydro-2H-pyrrolo[1,2-a][1,2,4] triazino [2,3-c]quinazoline-5a(6H)carboxylic Acids and their Salts – a Promising Class of Anti-inflammatory Agents
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Hybrid-Compounds Against Trypanosomiases
Current Drug Targets Docking-Based Virtual Screening: Recent Developments
Combinatorial Chemistry & High Throughput Screening Meet Our Editorial Board Member
Medicinal Chemistry History and Global Status of the New Coronavirus Covid-2019 and Aspects of Previous Infections of SARS-CoV and MERS-CoV: A Systematic Review
Coronaviruses Expression of Peptide Transporters on the Rabbit Retina: A Strategy to Improve Retinal Delivery of Ganciclovir
Letters in Drug Design & Discovery AMPA Glutamate Receptors and Neuropathic Pain
Mini-Reviews in Medicinal Chemistry Enhanced Production of β-Xylosidase from Aspergillus Niger ADH-11 and Development of Synergistic Enzyme Cocktail for Saccharification of Sugarcane Bagasse
Current Biotechnology Targeting the Akt Kinase to Modulate Survival, Invasiveness and Drug Resistance of Cancer Cells
Current Medicinal Chemistry Relaxin-Like Peptides in Neoplastic Lesions
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents From Laptop to Benchtop to Bedside: Structure-based Drug Design on Protein Targets
Current Pharmaceutical Design DC-SIGN Antagonists, a Potential New Class of Anti-Infectives
Current Medicinal Chemistry Synthesis of Novel Laurenditerpenol Analogues and their Evaluation as HIF-1 Activation Inhibitors
Letters in Organic Chemistry Antifungal Therapy Used in Central Nervous System Fungal Infections
Central Nervous System Agents in Medicinal Chemistry