Abstract
A pharmacophore model does not describe a real molecule or a real association of functional groups but illustrates a molecular recognition of a biological target shared by a group of compounds. Pharmacophores also represent the spatial arrangement of essential interactions in a receptor-binding pocket. Structure based pharmacophores (SBPs) can work both with a free (apo) structure or a macromolecule-ligand complex (holo) structure. The SBP methods that derive pharmacophore from protein-ligand complexes use the potential interactions observed between ligand and protein, whereas, the SBP method that aims to derive pharmacophore from ligand free protein, uses only protein active site information. Therefore SBPs do not encounter to challenging problems such as ligand flexibility, molecular alignment as well as proper selection of training set compounds in ligand based pharmacophore modeling. The current review deals with 'Hot Spot' analysis of binding site to feature generation, several approaches to feature reduction, and considers shape and excluded volumes to SBP model building. This review continues to represent several applications of SBPs in virtual screening especially in parallel screening approach and multi-target drug design. Also it reports the applications of SBPs in QSAR. This review emphasizes that SBPs are valuable tools for hit to lead optimization, virtual screening, scaffold hopping, and multi-target drug design.
Keywords: Hot spot, Multi-target drug design, Parallel screening, QSAR, Shape and excluded volumes, Structure based pharmacophores.
Current Topics in Medicinal Chemistry
Title:Methods and Applications of Structure Based Pharmacophores in Drug Discovery
Volume: 13 Issue: 9
Author(s): Somayeh Pirhadi, Fereshteh Shiri and Jahan B. Ghasemi
Affiliation:
Keywords: Hot spot, Multi-target drug design, Parallel screening, QSAR, Shape and excluded volumes, Structure based pharmacophores.
Abstract: A pharmacophore model does not describe a real molecule or a real association of functional groups but illustrates a molecular recognition of a biological target shared by a group of compounds. Pharmacophores also represent the spatial arrangement of essential interactions in a receptor-binding pocket. Structure based pharmacophores (SBPs) can work both with a free (apo) structure or a macromolecule-ligand complex (holo) structure. The SBP methods that derive pharmacophore from protein-ligand complexes use the potential interactions observed between ligand and protein, whereas, the SBP method that aims to derive pharmacophore from ligand free protein, uses only protein active site information. Therefore SBPs do not encounter to challenging problems such as ligand flexibility, molecular alignment as well as proper selection of training set compounds in ligand based pharmacophore modeling. The current review deals with 'Hot Spot' analysis of binding site to feature generation, several approaches to feature reduction, and considers shape and excluded volumes to SBP model building. This review continues to represent several applications of SBPs in virtual screening especially in parallel screening approach and multi-target drug design. Also it reports the applications of SBPs in QSAR. This review emphasizes that SBPs are valuable tools for hit to lead optimization, virtual screening, scaffold hopping, and multi-target drug design.
Export Options
About this article
Cite this article as:
Pirhadi Somayeh, Shiri Fereshteh and Ghasemi Jahan B., Methods and Applications of Structure Based Pharmacophores in Drug Discovery, Current Topics in Medicinal Chemistry 2013; 13 (9) . https://dx.doi.org/10.2174/1568026611313090006
DOI https://dx.doi.org/10.2174/1568026611313090006 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
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
- 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
-
Matrix Metalloproteinases as Potential Targets in the Venous Dilation Associated with Varicose Veins
Current Drug Targets Crosstalk between Gut Microbiota and Central Nervous System: A Focus on Alzheimer's Disease
Current Alzheimer Research Src Family Kinases as Potential Therapeutic Targets for Malignancies and Immunological Disorders
Current Medicinal Chemistry Exercise as Treatment for Neuropathy in the Setting of Diabetes and Prediabetic Metabolic Syndrome: A Review of Animal Models and Human Trials
Current Diabetes Reviews Anticancer Therapeutic Strategies Based on CDK Inhibitors
Current Pharmaceutical Design Hydroxychloroquine Sulfate (Plaquenil): A Possible Candidate for Pandemic SARS-CoV-2 or (COVID-19) ?
Coronaviruses Nanocrystals as Effective Delivery Systems of Poorly Water-soluble Natural Molecules
Current Medicinal Chemistry Optimizing Antitumor Efficacy and Adverse Effects of Pegylated Liposomal Doxorubicin by Scheduled Plasmapheresis: Impact of Timing and Dosing
Current Drug Delivery Current Molecular Understanding and Future Treatment Strategies for Pathologic Ocular Neovascularization
Current Molecular Medicine An Overview of Nanoformulated Nutraceuticals and their Therapeutic Approaches
Current Nutrition & Food Science Medical Image Processing Technology for Diagnosing and Treating Cancers
Recent Patents on Biomedical Engineering (Discontinued) Trojan Microparticles Potential for Ophthalmic Drug Delivery
Current Medicinal Chemistry Research Trends in Plant-Derived Oligomers for Health Applications
Current Nutraceuticals Learning from Nature: Bioinspired Strategies Towards Antimicrobial Nanostructured Systems
Current Topics in Medicinal Chemistry Paclitaxel Resistance: Molecular Mechanisms and Pharmacologic Manipulation
Current Cancer Drug Targets Targeting Transcription Factors for Cancer Therapy
Current Pharmaceutical Design Blockade of Insulin-Like Growth Factor Type-1 Receptor with Cixutumumab (IMC-A12): A Novel Approach to Treatment for Multiple Cancers
Current Drug Targets Telomeric G-Quadruplex Architecture and Interactions with Potential Drugs
Current Pharmaceutical Design Personalized Peptide Vaccine for Treatment of Advanced Cancer
Current Medicinal Chemistry Aminophosphonic Acids of Potential Medical Importance
Current Medicinal Chemistry - Anti-Cancer Agents