Abstract
The question of how and why a small molecule binds to a protein is central to ligand-based drug discovery. The traditional way of approaching these questions is pharmacophore analysis. However, pharmacophores as usually applied lack quantitation and subtlety. An improvement is to consider the electrostatic and steric fields of the ligand directly. Molecular fields provide a rich view of the potential interactions that a molecule can make and can be validated through experimental data on molecular interactions and through quantum mechanics calculations. A technique is presented in this review for comparing molecules using molecular fields and assigning similarity scores. This high information content method can be used to align molecules for SAR analysis, to determine the bioactive conformation from ligand data, and to screen large libraries of compounds for structurally unrelated actives. An extension to allow interactive exploration of chemistry space via bioisostere analysis is also reviewed. Examples from the literature showing the success of these methods are presented, and future directions discussed.
Keywords: Molecular field, pharmacophore, alignment, QSAR, bioactive conformation, virtual screening, bioisostere, ligand based design, molecular design, docking
Current Computer-Aided Drug Design
Title: High Content Pharmacophores from Molecular Fields: A Biologically Relevant Method for Comparing and Understanding Ligands
Volume: 7 Issue: 3
Author(s): Timothy J. Cheeseright, Mark D. Mackey and Robert A. Scoffin
Affiliation:
Keywords: Molecular field, pharmacophore, alignment, QSAR, bioactive conformation, virtual screening, bioisostere, ligand based design, molecular design, docking
Abstract: The question of how and why a small molecule binds to a protein is central to ligand-based drug discovery. The traditional way of approaching these questions is pharmacophore analysis. However, pharmacophores as usually applied lack quantitation and subtlety. An improvement is to consider the electrostatic and steric fields of the ligand directly. Molecular fields provide a rich view of the potential interactions that a molecule can make and can be validated through experimental data on molecular interactions and through quantum mechanics calculations. A technique is presented in this review for comparing molecules using molecular fields and assigning similarity scores. This high information content method can be used to align molecules for SAR analysis, to determine the bioactive conformation from ligand data, and to screen large libraries of compounds for structurally unrelated actives. An extension to allow interactive exploration of chemistry space via bioisostere analysis is also reviewed. Examples from the literature showing the success of these methods are presented, and future directions discussed.
Export Options
About this article
Cite this article as:
J. Cheeseright Timothy, D. Mackey Mark and A. Scoffin Robert, High Content Pharmacophores from Molecular Fields: A Biologically Relevant Method for Comparing and Understanding Ligands, Current Computer-Aided Drug Design 2011; 7 (3) . https://dx.doi.org/10.2174/157340911796504314
DOI https://dx.doi.org/10.2174/157340911796504314 |
Print ISSN 1573-4099 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6697 |
- 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
Related Articles
-
Selenium and Iodine in Autoimmune Thyroiditis
Endocrine, Metabolic & Immune Disorders - Drug Targets The Gut Mucosa as a Site for Induction of Regulatory T-Cells
Current Pharmaceutical Design Prospectives of Solid Self-microemulsifying Systems in Novel Drug Delivery
Current Drug Delivery Bugs as Drugs: Understanding the Linkage between Gut Microbiota and Cancer Treatment
Current Drug Targets Demographic, Clinical, and Investigational Characteristics of COVID-19- related Guillain-Barré Syndrome with Differences from Typical and Another Virus-related Guillain-Barré Syndrome
Infectious Disorders - Drug Targets CX3CL1/CX3CR1 Axis, as the Therapeutic Potential in Renal Diseases: Friend or Foe?
Current Gene Therapy Epigenetics in Ocular Diseases
Current Genomics Neurobiology of Alzheimer’s Disease: Integrated Molecular, Physiological, Anatomical, Biomarker, and Cognitive Dimensions
Current Alzheimer Research Decreasing the Metastatic Potential in Cancers - Targeting the Heparan Sulfate Proteoglycans
Current Drug Targets Editorial [Hot Topic: Fracture Risk Associated with Prescribed Medication (Guest Editor: Peter Vestergaard) ]
Current Drug Safety Adiponectin as a Regulator of Vascular Redox State: Therapeutic Implications
Recent Patents on Cardiovascular Drug Discovery A Systematic Review and Meta-analysis Investigating the Association Between Bone Marrow Lesions in People with Osteoarthritis
Current Rheumatology Reviews Predictability of Sustained Virological Response to Pegylated Interferon Alpha-2b Plus Ribavirin Therapy by Week-8 Viral Response in HIVPositive Patients with Chronic Hepatitis C Virus Infection
Current HIV Research Synthetic Lethal Interactions in Cancer Therapy
Current Cancer Drug Targets Monitoring Circulating Nitric Oxide Levels in Infants with Bronchopulmonary Dysplasia for Disease Activity
Current Pediatric Reviews Lipoprotein(a): Medical Treatment Options for an Elusive Molecule
Current Pharmaceutical Design Is Nephrogenic Systemic Fibrosis a Disease of Fibrocytes?
Current Rheumatology Reviews Genetic and Molecular Basis of QTL of Diabetes in Mouse: Genes and Polymorphisms
Current Genomics Safety and Efficacy of Tocolytics for the Treatment of Spontaneous Preterm Labour
Current Pharmaceutical Design The Mammalian Innate Immune System: Potential Targets for Drug Development
Current Drug Targets - Immune, Endocrine & Metabolic Disorders