1. Definition: Structure-Activity Relationship (SAR) is a method used in medicinal chemistry to understand and predict the effect of molecular structure on the activity of a substance.
2. Drug Design: SAR is a vital process in the design and development of therapeutic drugs, and it helps in optimizing the desirable and minimizing the undesirable properties of a molecule.
3. Quantitative and Qualitative Analysis: SAR provides both quantitative and qualitative means to correlate the chemical or structural characteristics of a molecule with its biological activity.
4. Molecular Modifications: SAR involves making systematic modifications to a molecule's structure and assessing how these changes impact the molecule's behavior.
5. Pharmacophore Model: The pharmacophore model is a key concept in SAR, representing the ensemble of steric and electronic features that ensure optimal interactions with a specific biological target and trigger (or block) its biological response.
6. Bioisosteres: In SAR, bioisosteres are used to create molecular analogs with similar biological activities. They are chemical substituents or groups with similar physical or chemical properties producing broadly similar biological properties to another chemical compound.
7. Computational Methods: Modern SAR relies heavily on computational methods and algorithms to predict and understand how changes in molecular structure will affect the activity of the molecule.
8. Machine Learning in SAR: Machine learning techniques have been increasingly used to analyze large datasets and generate predictive SAR models.
9. QSAR: Quantitative Structure-Activity Relationship (QSAR) is a type of SAR that uses regression or classification to create predictive models. QSAR focuses on the relationship between calculated or experimentally determined properties (descriptors) of molecules and their experimentally determined biological activities.
10. Bioavailability: SAR helps to optimize the bioavailability of drugs by modifying their chemical structure to improve absorption, distribution, metabolism, and excretion (ADME) properties.
11. Toxicity and Side Effects: Through SAR, researchers can identify structural features that contribute to toxicity and undesirable side effects and attempt to eliminate them.
12. Hit-to-Lead Optimization: SAR is used in the hit-to-lead phase of drug discovery, where promising compounds ("hits") are optimized to become "lead" compounds for further development.
13. Cheminformatics: Cheminformatics tools are integral to SAR, assisting in data analysis and visualization, predictive model generation, and virtual screening.
14. Drug-Target Interactions: Understanding the interaction between a drug and its target is crucial in SAR. This includes the study of binding affinities, active site interactions, and conformational changes.
15. Desirable Drug Properties: SAR helps to optimize various properties of a drug, including potency, selectivity, and stability.
16. Molecular Docking: Molecular docking, a method that predicts the preferred orientation of one molecule to a second when bound to each other, is frequently used in SAR studies to predict the structure of the complex formed and to understand intermolecular interactions between two molecules.
17. Ligand Efficiency Metrics: Ligand efficiency, a measure of how well a compound uses its atoms to bind to its target, is often used in SAR studies to assess the quality of hits and leads.
18. SAR Paradox: A concept in SAR, the "SAR paradox," refers to the phenomenon that minor structural changes can lead to major changes in biological activity.
19. Fragment-Based Drug Design (FBDD): FBDD is a common strategy in SAR, which involves identifying small chemical fragments, which may bind only weakly to the biological target, and growing, merging, or linking them to produce a lead with improved binding.
20. Multi-target SAR (mtSAR): In mtSAR, a single compound is optimized for activity against multiple targets, which can be useful in diseases where multiple targets are involved.
21. Rule of Five: The Lipinski's Rule of Five is a rule of thumb in drug design for predicting absorption or permeation, often used in the context of SAR.
22. Drug Resistance: SAR can help to understand how minor structural changes in a target molecule (such as a protein in a pathogen) can lead to drug resistance.
23. High-throughput Screening (HTS): HTS is a method for scientific experimentation especially used in drug discovery and relevant to the methods of SAR for the purpose of hit identification.
24. Molecular Dynamics (MD): MD simulations are often used in conjunction with SAR to study the dynamic behavior of bio-molecules and to understand the conformational changes upon drug binding.
25. SAR Studies Limitations: Despite the advances, SAR studies have limitations such as the need for high-quality data, the complexity of biological systems, the time and cost involved in synthesizing and testing modified compounds, and the fact that the effects of certain molecular modifications can be unpredictable.