QSAR.pptx..............................................

1. QSAR Padma Bhavani Assistant Professor RBVRR WOMEN’S COLLEGE OF PHARMACY

2. Introduction Drug discovery and development is a process aims to design safe and effective medications to improve life’s quality and to reduce suffering to minimum However, the process is very complex, time consuming, and resource intensive, requiring multi-disciplinary expertise and innovative approaches Rational drug design methods minimize the time and cost needed in drug designing process in comparison to traditional drug discovery methods 03-04-2021 Padma Bhavani, Assistant Professor, RBVRR WOMEN'S COLLEGE OF PHARMACY 2

3. Drug Design Drug design can be divided in two groups Structure based drug design (SBDD) and Ligand based drug design (LBDD) SBDD is the approach applying the structural information of the drug target to develop its inhibitor LBDD is used in the absence of the receptor 3D information and it relies on molecules bind to the biological target of interest 03-04-2021 Padma Bhavani, Assistant Professor, RBVRR WOMEN'S COLLEGE OF PHARMACY 3

4. Definition Quantitative structure-activity relationship (QSAR) It is a widely used approach in ligand based drug designing processes The aim of this method is to optimize the existing leads in order to improve their biological activities and physico -chemical properties Also, to predict the biological activities of untested and sometimes yet unavailable compounds 03-04-2021 Padma Bhavani, Assistant Professor, RBVRR WOMEN'S COLLEGE OF PHARMACY 4

5. QSAR It is used to design and identify new inhibitors de novo or to optimize absorption, distribution, metabolism, excretion and toxicity profile of identified molecules from various sources QSAR is a cheaper alternative than the medium throughput in vitro and low throughput in vivo assays QSAR models are regarded as a scientifically credible tool for predicting and classifying the biological activities of untested compounds, drug resistance, toxicity prediction and physicochemical properties prediction 03-04-2021 Padma Bhavani, Assistant Professor, RBVRR WOMEN'S COLLEGE OF PHARMACY 5

6. Principle The QSAR methodology is based on the concept that the differences observed in the biological activity of a series of compounds can be quantitatively correlated with differences in their molecular structure As a result, biological activities and functions of molecules relate to specific molecular descriptors Specific regression techniques can be used to estimate the relative roles of those descriptors contributing to the biological effect QSAR studies quantitatively correlate the relationships between chemical structure alterations and respective changes in biological endpoint 03-04-2021 Padma Bhavani, Assistant Professor, RBVRR WOMEN'S COLLEGE OF PHARMACY 6

7. QSAR QSAR mean computerized statistical method which helps to explain the observed variance in the structure changes caused by the substitution Biological activity exhibited by a series of compounds is a function of various physio-chemical properties It shows that certain physio-chemical properties are favorable to the concern activity A major goal of QSAR studies is to find a mathematical relationship between the activity or property under investigation, and one or more descriptive parameters or descriptors related to the structure of the molecule 03-04-2021 Padma Bhavani, Assistant Professor, RBVRR WOMEN'S COLLEGE OF PHARMACY 7

8. QSAR Development Process Step 1: Entry of the molecular structures and generation of the 3-D models Step 2: Generation of the molecular structure descriptors Step 3: Selection of the most important descriptors Step 4: Generation of the QSAR models using the descriptor sets Step 5: Validate the model by predicting the activity of compounds in the external prediction set The results obtained by the predictions should be compared to those achieved for the training set and cross validation set to easily understand model’s fitness level 03-04-2021 Padma Bhavani, Assistant Professor, RBVRR WOMEN'S COLLEGE OF PHARMACY 8

9. Software There are a lot of software available for QSAR development and they are either commercial or free These include specialized software for drawing chemical structures, interconverting chemical file formats, generating 3D structures, calculating chemical descriptors, developing QSAR models, and general-purpose software that have all the necessary components for QSAR development 03-04-2021 Padma Bhavani, Assistant Professor, RBVRR WOMEN'S COLLEGE OF PHARMACY 9

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11. Molecular descriptors Molecular descriptors are final products of mathematical procedures transforming chemical information encoded within a molecular structure to a numerical representative 03-04-2021 Padma Bhavani, Assistant Professor, RBVRR WOMEN'S COLLEGE OF PHARMACY 11

12. Applications Drug discovery often involves the use of QSAR to identify chemical structures that could have good inhibitory effects on specific targets and have low toxicity (non-specific activity) QSAR involves the prediction of partition coefficient log P, which is an important measure used in identifying " druglikeness " according to Lipinski's Rule of Five The QSAR equations can be used to predict biological activities of newer molecules before their synthesis 03-04-2021 Padma Bhavani, Assistant Professor, RBVRR WOMEN'S COLLEGE OF PHARMACY 12

13. Applications QSAR analysis involve the interactions of a family of molecules with an enzyme or receptor binding site QSAR can also be used to study the interactions between the structural domains of proteins Protein-protein interactions can be quantitatively analyzed for structural variations resulted from site-directed mutagenesis 03-04-2021 Padma Bhavani, Assistant Professor, RBVRR WOMEN'S COLLEGE OF PHARMACY 13

14. Reference Applications of QSAR Study in Drug Design International Journal of Engineering Research & Technology (IJERT) http://www.ijert.org ISSN: 2278-0181 IJERTV6IS060241 Published by : www.ijert.org Vol. 6 Issue 06, June - 2017 03-04-2021 Padma Bhavani, Assistant Professor, RBVRR WOMEN'S COLLEGE OF PHARMACY 14