Abstract
In silico drug discovery is a complex process requiring flexibility and ingenuity in method selection and a careful validation of work protocols. GPCR in silico drug discovery poses additional challenges due to the paucity of crystallographic data. This paper starts by reviewing selected GPCR in silico screening programs reported in the literature, including both structure-based and ligand-based approaches. Particular emphasis is given to library design, binding mode selection, process validation and compound selection for biological testing. Following literature review, we provide insights into in silico methodologies and process workflows used at EPIX and previously at PREDIX to drive over 20 highly successful screening and lead optimization programs performed since 2001. Applications of the various methodologies discussed are demonstrated by examples from recent programs that have not yet been published.
Current Topics in Medicinal Chemistry
Title: G Protein Coupled Receptors - In Silico Drug Discovery and Design
Volume: 10 Issue: 6
Author(s): I. Sela, G. Golan, M. Strajbl, D. Rivenzon-Segal, S. Bar-Haim, I. Bloch, B. Inbal, A. Shitrit, E. Ben-Zeev, M. Fichman, Y. Markus, Y. Marantz, H. Senderowitz and O. Kalid
Affiliation:
Abstract: In silico drug discovery is a complex process requiring flexibility and ingenuity in method selection and a careful validation of work protocols. GPCR in silico drug discovery poses additional challenges due to the paucity of crystallographic data. This paper starts by reviewing selected GPCR in silico screening programs reported in the literature, including both structure-based and ligand-based approaches. Particular emphasis is given to library design, binding mode selection, process validation and compound selection for biological testing. Following literature review, we provide insights into in silico methodologies and process workflows used at EPIX and previously at PREDIX to drive over 20 highly successful screening and lead optimization programs performed since 2001. Applications of the various methodologies discussed are demonstrated by examples from recent programs that have not yet been published.
Export Options
About this article
Cite this article as:
Sela I., Golan G., Strajbl M., Rivenzon-Segal D., Bar-Haim S., Bloch I., Inbal B., Shitrit A., Ben-Zeev E., Fichman M., Markus Y., Marantz Y., Senderowitz H. and Kalid O., G Protein Coupled Receptors - In Silico Drug Discovery and Design, Current Topics in Medicinal Chemistry 2010; 10 (6) . https://dx.doi.org/10.2174/156802610791111498
DOI https://dx.doi.org/10.2174/156802610791111498 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Ascorbic Acid in Postoperative Intensive Care Patients - Biochemical Aspects and Clinical Experience
Current Medicinal Chemistry Experimental Developments and Review of Recent Patents for the Repair of Skeletal Muscles by Methods of Regenerative Medicine
Recent Patents on Regenerative Medicine Atrial Fibrillation in Patients Undergoing Surgical Revascularization: An Update on Pharmacologic Prophylaxis
Cardiovascular & Hematological Agents in Medicinal Chemistry A PPAR-β/δ Agonist is Neuroprotective and Decreases Cognitive Impairment in a Rodent Model of Parkinson’s Disease
Current Neurovascular Research DL-3-n-Butylphthalide, an Anti-Oxidant Agent, Prevents Neurological Deficits and Cerebral Injury Following Stroke per Functional Analysis, Magnetic Resonance Imaging and Histological Assessment
Current Neurovascular Research The Role of ER Stress-Induced Apoptosis in Neurodegeneration
Current Alzheimer Research Impaired Myocardial MIF/AMPK Activation Aggravates Myocardial Ischemia Reperfusion Injury in High-Fat Diet-Induced Obesity
Endocrine, Metabolic & Immune Disorders - Drug Targets Melatonin and Its Therapeutic Potential in Neuroprotection
Central Nervous System Agents in Medicinal Chemistry Monitoring Circulating Nitric Oxide Levels in Infants with Bronchopulmonary Dysplasia for Disease Activity
Current Pediatric Reviews Curcumin Prevents Brain Damage and Cognitive Dysfunction During Ischemic-reperfusion Through the Regulation of miR-7-5p
Current Neurovascular Research Role of Oxidative and Nitrosative Stress, Longevity Genes and Poly(ADPribose) Polymerase in Cardiovascular Dysfunction Associated with Aging
Current Vascular Pharmacology The NF-kB Pathway as a Potential Target for Autoimmune Disease Therapy
Current Pharmaceutical Design Cross-Talk Between Mesenchymal Stem/Stromal Cells and Dendritic Cells
Current Stem Cell Research & Therapy Immunogenicity and Tumorigenicity of Pluripotent Stem Cells and their Derivatives: Genetic and Epigenetic Perspectives
Current Stem Cell Research & Therapy Subject Index to Volume 1
Current Vascular Pharmacology Connexin43 and Myocardial Ischemia-Reperfusion Injury
Cardiovascular & Hematological Disorders-Drug Targets The Heme Oxygenase System: Its Role in Liver Inflammation
Current Drug Targets - Cardiovascular & Hematological Disorders Ruthenium as an Effective Nitric Oxide Scavenger
Current Topics in Medicinal Chemistry Protective Effect of GSK-3β/Nrf2 Mediated by Dimethyl Fumarate in Middle Cerebral Artery Embolization Reperfusion Rat Model
Current Neurovascular Research PEDF & Stem Cells: Niche vs. Nurture
Current Drug Delivery