PY6009 - COMPUTER AIDED DRUG DESIGN (Syllabus) 2013-regulation Anna University

PY6009 - COMPUTER AIDED DRUG DESIGN (Syllabus) 2013-regulation Anna University

PY6009	COMPUTER AIDED DRUG DESIGN	LPTC

3003

OBJECTIVES:

The course aims to provide students with an understanding of the process of drug discovery and development through in-silico methods right from the identification of novel drug targets to the introduction of new drugs into clinical practice.
The objective of this course is to present the appropriate tools for such a modeling ranging from molecular mechanics, molecular dynamics over computer graphics, data visualization, De Novo Design and chemometrics to computer assisted synthesis design based on artificial intelligence.

UNIT I	MOLECULAR MECHANICS	9

Introduction to CADD, Techniques and Concepts Used In CADD. Molecular Recognition, Molecular Docking and Role of Solvents. Concept of Force Field in MM, molecular dynamics, molecular simulation, montecarlo, quantum mechanics semi empirical and empirical methods, applicability and limitations of a MM approach.

UNIT II	MOLECULAR MODELLING	9

Historical overview, Graphical representation of molecules, technologies and models, simplified representation, molecular surfaces, Corey-Puling-Koltun (CPK) / Vander Waals surface, Solvent accessible and excluded surface, Conolly surface, Electron Density Surface, Molecular volume, Molecular superimposition, molecular similarity, molecular skin, molecular shape descriptors and mapping of information on molecular surfaces.

UNIT III	CHEMOMETRICS	9

Origin and current status, multivariate data, definition and classification of data, preprocessing, distance between objects, latent variables, linear methods, projection of multivariate data, Principal Component Analysis, Multiple Linear Regression, Principle Component Regression, Partial Least Squares, nonlinear methods, Modelling methods, Classification methods, Linear discriminant analysis, validation tools, cross validation, bootstrapping, statistical indices

UNIT IV	2-D QSAR	9

Physicochemical descriptors in QSAR (Lipophilicity; clogP, polorizabilty; MR, Es, verloopsterimol parameter, electronic constants, ionization constant, HOMO, LUMO, and topological descriptors). Free-Wilson Model, Fugita-Ban Model, Hansch analysis. Comparison between Free-Wilson model and Hansch analysis. Molecular Connectivity Index (MCI)

UNIT V	3-D-QSAR: COMFA & CoMSIA	9

Introduction to 3-D QSAR, Comparative Molecular Field Analysis (CoMFA) methodology, steps in CoMFA analysis, derivation of CoMFA model, CoMFA coefficient maps, validation of results with relevant examples from recent literatures, CoMFA applications in drug design. Comparative Molecular Similarity Analysis (CoMSIA) : Introduction and Case studies

TOTAL : 45 PERIODS

OUTCOMES: The student able to

• Have an in-depth overview over the state-of-the art methods and techniques nowadays applied in CADD.
• Choose the appropriate for a given problem like, lead optimization, structure based design, investigation of ligand receptor interaction.
• Perform, understand, and interpret the results of the calculations and bring them in a publication ready form.

TEXT BOOKS:

1. Computer Aided Drug Design Edited by Thomas J Perun, Marcel Dekker: New York, NY.
2. Structure based Drug Design Pandi Veerapandian, Taylor and Francis
3. Smith and Williams Introduction to Principles of Drug Design and Action Edited by H. John Smith, Taylor and Francis
4. Textbook of Drug Design and Discovery Edited by PovlKrogsgard-Larson, Taylor and Francis
5. Molecular Modeling: Principles and Applications, Andrew R. Leach

REFERENCES:

1. Burger’s Medicinal Chemistry and Drug Discovery
2. Comprehensive Medicinal Chemistry. Vol IV.
3. G. Patrick. (2013) An Introduction to Medicinal Chemistry. Oxford University Press, UK.
4. D. C. Young. (2009) Computational Drug Design – A Guide for Computational and Medicinal Chemist. John Wiley & Sons, Inc., Hoboken, New Jersey.
5. A. Hinchliffe. (2008) Molecular Modelling for Beginners. John Wiley & Sons Ltd, England.