Fundamentals of Rational Drug Design

An Introduction to Molecular Interactions in Biological Systems   

This course examines biochemical and biophysical concepts of molecular interactions between ligands and their receptors and resulting applications for rational drug design. Many drugs are small ligand molecules that interact with macromolecular surfaces. Affinity and specificity of ligand binding are determined by molecular surface patterns, their chemical similarity and structural complementarity, and governed by non-covalent bonds that are electrostatic in nature. Our understanding of biological ligand-receptor systems leads the way to applications in the drug discovery process and the successful design of efficient, specific, and non-toxic small-molecule therapeutics.

Essential Reading

Protein Structures DNA and RNA Structure
Membrane Proteins and Ion Channels DNA Binding Proteins
Drugs and their receptors Drug - DNA interaction
Proteases and Enzyme Kinetics Self-assembly Systems

Read also about Cell Membranes as Therapeutic Targets

Lukas Buehler received a PhD in biochemistry from the University of Basel, Switzerland. He teaches biochemistry at the Division of Biology at UCSD and gained extensive research experience in protein biochemistry, electrophysiology, self-assembly systems, DNA microarray analysis, and drug discovery over many years of research at UCSD, the Scripps Research Institute, and the R.W.Johnson Pharmaceutical Research Institute. He is the owner of SciScript, Inc., a bioinformatics consulting company.

Drug Design, a column by Lukas Buehler for Pharmaceutical Discovery, (formerly PharmaGenomics) a trade publication for the pharmaceutical and biotechnology industry

Advanced Drug Discovery: Beyond Design.
PharmaGenomics, 2004 (July)24-26
   (read article)

From Ion Channels Flow Fresh Discovery Approaches.
PharmaGenomics, 2004 (February)16-19
   (read article)

Beyond Recognition.
PharmaGenomics, 2003, 3(8):26-30
 (read article)

What's in a Structure
PharmaGenomics, 2003, 3(5):20-21  (
read article)


Guidebook on Molecular Modeling in Drug Design
ed. by Claude Cohen; Academic Press, 1996

Covers molecular graphics tools, modeling of small molecules, computer  assisted lead design and drug discovery, modeling drug-receptor interaction, experimental techniques and data banks.

This lecture has been developed for UCSD Extension, Bioscience Program; For information on Bioscience classes at UCSD Extension, please visit

H o m e  

Copyright © 1999-2006 Lukas K. Buehler