Lock and Key

Chem 162A-B/262A-B

Drug Design

Acetylcholine receptor

Lecturer:

Dr. Kalju Kahn
Office: PSB-N 2623
Office hours: Mon 10:30-11:30 PM, and Tue 4:30-5:30 PM
Phone: 893-6157
E-mail: kalju@chem.ucsb.edu
Website: http://www.chem.ucsb.edu

Teaching Assistant

Mission statement

To teach principles that govern the process of modern drug discovery and development. Students in the course follow a path similar to that taken by real-life drug developers by learning important elements of the drug design process in a logical order.

About Chem 162A

Chem 162A, the first in the two-course series focuses on principles of rational drug design. Topics covered include target identification and validation technologies, generation and screening of chemical libraries for finding lead compounds, and modern medicinal chemistry approaches for ligand-based lead optimization. We will cover membrane-bound ion-channels and receptor proteins, and discuss strategies for finding agonists and antagonists for these types of targets.

About Chem 162B

The second course in the series, Chem 162B, will be taught in the Spring of 2012. The latter course focuses on structure-based drug design. It will outline experimental and computational methods for the study of ligand-protein complexes, and discuss how the knowledge of the three-dimensional structure of the active site helps in the lead optimization process. Chem 162B will also cover approaches used to design competitive and mechanism-based inhibitors based on the mechanistic understanding of enzyme catalysis. Finally, issues of pharmacokinetics and drug metabolism will be dealt with. Students are allowed to take Chem 162B/262B without taking Chem 162A/262B this academic year.

Schedule

      Lecture:        MWF 8:00-8:50		Place:  Phelps 1508 
      Computer Lab:   Open day access 		Place:  Chem 1153
Syllabus General information about the course. PDF
Textbook The Organic Chemistry of Drug Design and Drug Action by Richard B. Silverman (Second Edition) Amazon
Textbook An Introduction to Medicinal Chemistry (Fourth Edition) Amazon
Sample Lecture Target Validation. (No Password Needed) Warning: Large File PDF WAV
Last Years Drug Design 162A (by Dr. Kalju Kahn) website for Fall 2009 Link
Last Years Drug Design 162B (by Dr. Kalju Kahn) website for Winter 2010 Link
Exam Midterm Preparation Guide PDF
Exam Key Midterm Exam Key (Winter 2012) PDF
Exam Final Preparation Guide PDF
Exam Sample I Sample questions with answers from Spring 2004 PDF
Upload Submit your assignments as PDF files Link
Exam Key Chem 162A Final Key, Winter 2012 PDF

Lecture Notes

Course notes will be posted here before 7:30 a.m. of the lecture day. The lecture slides are password-protected. Contact your instructor to obtain the password.

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Notes Lecture Notes. Powerpoint Pages in PDF Acrobat
Jan 9 Overview of the course. History of Drug Design. PDF
Jan 11 Rational Drug Design: Overview of Approaches PDF
Jan 13 Diseases and the Biological Concept PDF
Jan 20-23 Target Validation: Principles PDF
Jan 23 Target Validation: Pre-Genomic Methods PDF
Jan 26 Target Validation: Post-Genomic Methods PDF
Jan 27 Target Validation Tutorial Link
Jan 30 Receptors as Drug Targets: General Overview PDF
Feb 1 Receptors as Drug Targets: Ion Channels PDF
Feb 3-6 Receptors as Drug Targets: GPCRs PDF
Feb 8 Study of Membrane Receptors PDF
Feb 13 Nuclear Hormone Receptors PDF
Feb 13 Assays PDF
Feb 15 Combinatorial Chemistry PDF
Feb 24 Ligand-based drug design and optimization PDF
Feb 27 Ligand-based drug design and optimization PDF
Feb 29 Optimization of ADME properties PDF
March 5-7 Fragment-based drug design and optimization PDF
March 9-12 QSAR PDF
April 2 Enzymes as Drug Targets PDF
April 4 Enzymes: General Features PDF
April 6 Enzymes: Principles of Catalysis PDF
Apr 9 Enzymes: Mechanism and Kinetics PDF
Apr 13 Modeling of chemical reactions and transition state analogs Link
Apr 16 Enzyme Inhibition PDF
Apr 18 Mechanism-Based Enzyme Inactivation PDF
Apr 20 Structure-Based Drug Design: Intermolecular Interactions PDF
Apr 23 Structure-Based Drug Design: Thermodynamics PDF
Apr 25 Visualization of Electrostatic Potential Surfaces Link
Apr 27 Structure-Based Drug Design: Protein Structure Analysis PDF
Apr 30 Structure-Based Drug Design: Docking PDF
May 4 Structure-based Drug Design: Docking Link
May 7-14 Structure-Based Drug Design: Modeling Protein Flexibility PDF
May 15-17 Pharmacokinetics and ADMET Challenges PDF
May 21 Drug Metabolism: Principles PDF
May 23 Drug Metabolism: P450 PDF
May 25 P450 Pharmacogenomics: Drug Toxicity and Drug-Drug Interactions PDF
May 30 Prodrugs and Drug Delivery PDF
June 1 Nucleic Acid Drugs PDF
June 4 Job Options, Marketplace, and FDA PDF

Required Literature

Literature Required reading in PDF Acrobat
General From Serendipity to Rational Drug Design PDF
History Drug Discovery: A Historical Perspective PDF
Future Drug Research: Myths, Hype and Reality PDF
Targets Antibacterial discovery strategy: GSK story PDF
Targets How many drug targets are there? PDF
Targets In Silico fishing for targets PDF
Receptors Principles: Receptor Theory in Pharmacology (Kenakin, 2004) PDF
Receptors Epibatidine: Impact on Nicotinic Receptor Research (Dukat & Glennon, 2003) PDF
Receptors Orphan GPCRs (Wise, Jupe, and Rees, 2004) PDF
Receptors How Antidepressants Block Neurotransmitter Reuptake PDF
CombiChem High-diversity combinatorial libraries (Weber, 2000) PDF
CombiChem Three-Component Synthesis of 2-Imidazolines (Orru et al, 2007) PDF
Ligand-Based Chemistry of 1,4-benzodiazepines (Sternbach, 1971) PDF
Ligand-Based Molecular Superposition (Miller, 1998) PDF
Ligand-Based Fragment-Based Drug Discovery (Erlanson, 2004) PDF
Ligand-Based Fragment-Based Drug Discovery (Erlanson, 2012) PDF
QSAR Some observations on classical QSAR (Topliss, 1993) PDF
QSAR From Narcosis to Hyperspace: The History of QSAR (Kubinyi, 2002) PDF
Enzymes Enzymes and Enzyme Inhibition (Kahn) PDF
Enzymes Transition State Binding PDF
Enzymes Enzymatic Transition State Theory PDF
Enzymes Protein Kinase Inhibitors PDF
SBDD Principles of Biomolecular Recognition PDF
SBDD The Process of Structure-Based Drug Design PDF
SBDD The Many Roles of Computation in Drug Discovery PDF
SBDD Protein-ligand docking: Current Status and Future Challanges PDF
SBDD High-throughput docking PDF
SBDD High-throughput docking: thyroid hormone receptor PDF
Metabolism Coupled Bioreactor-HPLC-MS metabolite analysis of SERMs PDF
Prodrugs Lessons Learned from Marketed and Investigational Prodrugs PDF
Drug Delivery Targeted Nanoparticles for Cancer Therapy PDF

Suggested Literature

Suggested literature can be found now on a separate page

Assignments

The assignments are posted one week before the due date. Answers shall be submitted electronically no later than the midnight of the due date.

Assignments PDF files Acrobat
1 Enzymes. Catalysis and Inhibition. PDF
4 Pharmacokinetics, ADMET Challenges PDF
5 Drug Metabolism, Prodrugs, Drug Delivery PDF

Answer Keys

The assignment keys are typically posted one week after the due date.

Keys PDF files Acrobat
1 Enzymes: Mechanisms & Inhibition PDF
2 Electrostatic Potential Maps: Small Molecules Link
2 Visualization of Chorismate Mutase Active Sites PDF
3 Target-Based Drug Design: Docking Link
4 Pharmacokinetics, ADMET Challenges PDF
5 Drug Metabolism, Prodrugs, Drug Delivery PDF

Drug Design Project

The project milestone guides are typically posted week and a half before they are due.

Project Tips General Guidelines to Project Development PDF

Glossary

Students in this course encounter many terms which have specific meaning in the context of drug design and medicine. You may find our glossary helpful when reading some of the assigned papers. If you encounter a term that is not in this dictionary, you could try a specialized medicinal chemistry glossary at www.chem.qmw.ac.uk/iupac/medchem ,an on-line dictionary at www.dictionary.com or an on-line encyclopedia at www.wikipedia.com . Feel free to send any additions and suggestions to Kalju Kahn

Molecular Visualization Resources

PyMOL Home Page
Biomolecular Images for Teaching with PyMOL
SYBYL Tutorial
Short List of Programs

Useful (and used) drug design links

Modern Drug Discovery
Nature Reviews Drug Discovery
Drug Discovery and Development
Drug Design Lecture Notes by Dr. Hugo Kubinyi
Oxford Drug Resistance Group Lectures
Calcium Channel Blockers
Brain Chemistry
Dr. Andrew Boa lecture notes
An Overview of Marine Drug Discovery

Useful science links

Electronic Journals at UCSB
Google Web Search Engine
Biology Workbench
ExPASy Molecular Biology Server
Protein Data Bank
Periodic Table of the Elements
Cell and Molecular Biology Protocols Online

UCSB links

UCSB General Catalog
UCSB Campus Map
UCSB Gold Login
UCSB Umail Access
UCSB Environmental Health and Safety




Course materials by Dr. Kalju Kahn, Department of Chemistry and Biochemistry, UC Santa Barbara. 2004-2012