Structure Activity Relationship (SAR) Analysis
Overview of SAR Analysis
The earliest study of structure-activity relationship (SAR) speculated the relationship between the structure and activity of physiologically active substances, and then inferred the structure of the active site of the target enzyme and designed a new structure of the active substance. With the development of information technology, at present, the quantitative structure-activity relationship (QSAR) with the computer as an auxiliary tool has become the main direction of structure-activity relationship research. The QSAR has also become one of the important methods for rational drug design.
Fig. 1 Overview of QSAR/QSPR modeling. (Patel, et al. 2014)
Quantitative Structure-Activity/Property Relationship (QSAR/QSPR) is the application of chemical theory calculation methods and various mathematical statistical analysis methods to quantitatively describe and study the relationship between the structure and activity/property of organic objects, and establish a mathematical model of QSAR/QSPR. Once the reliable QSAR/QSPR model is established, it can be used to predict the various properties of the new compound after testing for predictive power. The basic assumption in the QSAR/QSPR study is that the characters or biological activity of a compound can be expressed as a function of the chemical structure. That is, a mathematical model can be used to combine theoretical calculations and statistical analysis to study the quantitative relationship between the structure of a series of compounds and their properties.
Peptides have gained renewed interest as candidate therapeutics. However, to bring them to a broader clinical use, challenges such as the rational optimization of their pharmacological properties remain.
Creative Peptides has developed a reliable procedure for SAR analysis of peptides, we can provide global customers with the analysis of peptides based on our excellent technology.
The 3D-QSAR method used by Creative Peptides is more physicochemically meaningful and can indirectly reflect the non-bond interaction characteristics between the peptide and the target. Creative Peptides uses a method of comparative molecular similarity indices analysis (CoMSIA) for peptide analysis, the steps of which include:
- Determining the active conformation of a peptide: the optimal conformation of a peptide is obtained by molecular mechanics or quantum chemical procedures.
- Molecular superposition: the optimal conformation of the most active compound is used as a template, and the remaining molecules overlap with the corresponding atoms on the template molecular skeleton to minimize the root mean square deviation of the intermolecular overlap.
- Calculating interaction energy
- Partial least squares analysis
- Finally displayed in 3D graphics
1. Patel, H. M., Noolvi, M. N., Sharma, P., Jaiswal, V., Bansal, S., & Lohan, S., et al. (2014). Quantitative structure–activity relationship (qsar) studies as strategic approach in drug discovery. Medicinal Chemistry Research,23(12), 4991-5007.
2. Pripp, A. H., Isaksson, T., Stepaniak, L., Sorhaug, T., & Ardo, Y. (2005). Quantitative structure activity relationship modelling of peptides and proteins as a tool in food science. Trends in Food Science & Technology,16(11), 484-494.
3. Arodola, O. A., & Soliman, M. E. (2017). Quantum mechanics implementation in drug-design workflows: does it really help?. Drug Des Devel Ther, Volume 11, 2551-2564.