On line quizzes are multiple choice questions on the previous 2 weeks work.

The report and presentation is a major work that you will start preparing in week 5 and complete in week 13.  It involves a written report and a powerpoint presentation (15 minutes)

The final exam is a 3 hr written exam

The weekly classes are a participation hurdle and failure to participate in at least 10 of the 13 weekly classes will result in you failing CBMS842.  If you are unable to attend a class, please contact Peter Karuso (peter.karuso@mq.edu.au) immediately.  In addition, you must submit a Special Consideration request at ask.mq.edu.au to justify your absence.

Your marks (in-class and online quizzes, report and presentation) will be placed on the CBMS842 web site. 

Your final grade will be based on the mark from the aggregation of the individual assessments, with 50% or greater needed overall for a pass.

Medical certificates or official documents must be lodged as part of a disruption to studies request at ask.mq.edu.au as soon as possible if you are absent for any of the weekly classes, assessment tasks or miss the due date for any of the on-line tasks.  If your reason is regarded as valid for missing the in-class quizzes, you will be given an average of the other quizzes done; with the on-line quizzes an extension of time will be provided if the disruption to studies request is approved.  If you miss the final exam for a valid reason, a supplementary exam will be provided.  Any assessment tasks not submitted on time that does not get approval through the disruption to studies request will get a 10% deduction of marks for every weekday late.

Final Examination Details:  The examination timetable will be available in Draft form approximately eight weeks before the commencement of the examinations and in final form approximately four weeks before the commencement of the examinations.  You are expected to present yourself for examination at the time and place designated by the University in the Examination Timetable.  This could be any day after the final week of semester and up until the final day of the official examination period.  It is Macquarie University policy to not set early examinations for individuals or groups of students.  All students are expected to ensure that they are available until the end of the teaching semester, that is, the final day of the official examination period.  NOTE:  If you apply for a supplementary examination, you must make yourself available for the week of Dec 4-8.  If you are not available at that time, there is no guarantee an additional examination time will be offered. Specific examination dates and times will be determined at a later date.  

The only exception to sitting an examination at the designated time is because of documented illness or unavoidable disruption.  Absence from the final exam will result in a grade of F except in the case of a genuine medical emergency or misadventure as defined by the University (see below).  In these circumstances you should apply for a Supplementary Exam at ask.mq.edu.au.

This is a self taught unit using the "molecular conceptor" and MOE software.  Each week a set number of tasks are assigned and assessed. There is no text book set for this unit but the material in the CBMS606 text book (Patrick, "Medicinal Chemistry", 5th Ed) is assumed knowledge.

WEEK 1 – Introduction to drug design

Introduction to Drug Discovery

1. From the Origin of Medicines to Today
2. Revolutions that Changed Drug Discovery
3. In-Silico Technologies
4. The Drug Discovery Process
5. Rational Drug Design Strategy

Principles of Rational Drug Design

1. Rational Drug Design
2. Pharmacophore-Based Design
3. Receptor-Based Design
4. Integration in a Global Perspective
5. Challenge of the Genomics Era
6. Typical Projects

WEEK 2 – Molecular basis of drugs

Molecular Geometry

1. 2D/3D
2. Conformers
3. Torsion Angles
4. Conformational Complexity
5. Ratio of Conformers

Molecular Energies

1. Introduction
2. Thermodynamics
3. Kinetics
4. Modelling in Drug Design
5. How to Calculate Energies
6. Quantum Mechanics
7. Molecular Mechanics

Molecular Graphics

1. Visualisation
2. Editing and Manipulation
3. Surfaces and Volumes
4. Visualising Interactions

WEEK 3 – Library design

Library Design

1. Introduction
2. The Basis of a Good Scaffold
3. Scaffold Selection and Design
4. Focused and Diverse Strategies
5. Measuring Distances Between Molecules
6. Increasing the Quality of a Library
7. Example of Library Analysis

Case Studies in Library Design

1. Case Study-1: CDK2 Inhibitors
2. Case Study-2: DHFR Inhibitors

WEEK 4 - Structural bioinformatics and protein structure

Protein Structure

1. Structural and Functional Diversity of Proteins
2. Amino Acids: Building Blocks of Proteins
3. From Amino Acids to Proteins
4. Geometry of Proteins and Peptides
5. Protein Structure Overview
6. Primary Structure
7. Secondary Structure
8. Tertiary Structure
9. Quaternary Structure
10. Structural Classification of Proteins

Structual Bioinformatics

1. Introduction to Structural Bioinformatics
2. Biomolecular Properties
3. Assembly of Biomolecules

WEEK 5 – Structure-activity relationships (SAR)

Structure Activity Relationships (SAR)

1. Introduction
2. Probing H-Bond Interactions
3. Probing Ionic Interactions
4. Probing Hydrophobic Interactions
5. Probing Other Interactions
6. Modifications to Alter the Geometry of the Ligand
7. Complexity of SAR Analyses

WEEK 6 – SAR case studies

Case Studies in SAR Analyses

1. Case Study-1: Banyu Example
2. Case Study-2: Dioxobenzothiazole Example
3. Case Study-3: EGF-R Kinase Inhibitors
4. Case Study-4: Nifedipine Example
5. Case Study-5: Carbonic Anhydrase Example
6. Case Study-7: Anilino-Quinazoline Example

Case Studies in Advanced Analog Design

1. Case Study-8: Salicylamide Mimics

WEEK 7 – Molecular docking

Molecular Docking: Principles and Methods

1. Introduction to Computational Docking
2. The Docking Problem
3. Scoring Methods
4. Uses of Docking in Research
5. Futures and Perspectives

WEEK 8 – Structure based design

Introduction to Protein-Ligand Binding

1. Introduction
2. Analytical Process
3. Principles of Analysis
4. Example of Tight Interactions
5. Receptor and Ligand Flexibility
6. Role of the Solvent
7. Prediction of Binding Modes
8. Methods for Analysing Binding
9. Conclusion

Principles of Structure-Based Design

1. Introduction
2. Eight Golden Rules
3. Four Design Methods
4. Analog Design
5. Database Searching
6. Manual Design
7. Another Iteration
8. Success Story
9. Conclusion

WEEK 9 – Structure based design & case studies

Case Studies in Structure-Based Design

1. Case Study-1: Phenyl Imidazoles
2. Case Study-2: BACE-1 Inhibitors
3. Case Study-3: Factor Xa Inhibitors
4. Case Study-4: Kinase Inhibitors

Case Studies of Docking in Drug Discovery

1. Case Study-1: Pyrimidin-4-yl-ureas for Kinase Inhibition
2. Case Study-2: Inhibition of CHK1
3. Case Study-3 Thrombin Inhibitors

Analyses of Protein-Ligand Complexes

1. Rotamase Inhibitors
2. Intercalating Antibiotics
3. Sialidase Inhibitors

WEEK 10 – Ligand based design A

Principles in Pharmacophore Elucidation

1. Introduction
2. Analytical Process
3. Simple Case
4. Typical Example
5. Complexity Levels
6. Principles of Analysis
7. Conformational Control
8. Managing Hypotheses
9. Receptor Mapping
10. Two Generations of Pharmacophores
11. Summary

Ligand-Based Approaches

1. Introduction
2. Four Design Methods
3. Chemical Modifications

WEEK 11 – Ligand based design B & case studies

Ligand-Based Approaches

1. Database Searching
2. De-Novo Design
3. Examples of Design
4. Conclusion

Examples of Pharmacophores

1. ACE Inhibitors
2. Serotonin Antagonists
3. Dopamine D-2 Antagonists
4. Beta-Lactam Antibiotics

Case Studies in Ligand-Based Design

1. Case Study-1: Aromatase Inhibitors
2. Case Study-2: Substance P Antagonists
3. Case Study-3: Tricyclic Antidepressants
4. Case Study-4: Morphinan Analgesics

WEEK 12 – QSAR (optional)

QSAR: Principles and Methods

1. Introduction to QSAR
2. The Foundations of QSAR
3. Design of a QSAR Model
4. Compounds Selection: Step 1
5. Descriptors Selection: Step 2
6. Deriving the Equation: Step 3
7. Validating the Model: Step 4

Case Studies in QSAR and 3d-QSAR

1. Case Study-1: QSAR of Capsaicin Analogs

MOE WORKSHOPS

1. Introduction to MOE
2. Building Molecules
3. 3D Visualisations
4. Structure based design
5. Docking
6. Ligand based design
7. Protein Ligand Interaction footprints

There are no major changes since last time.