Chem 162/262 Final Exam Guide Fall 2005 (Kahn) The final exam in Chem 162/262 will test your knowledge of the material that was covered after the midterm; the final will also test your understanding of topics covered in the whole course. You can demonstrate your knowledge by answering specific questions (e.g. draw a double-reciprocal plot illustrative of competitive enzyme inhibition). You can demonstrate your understanding by explaining what approaches and techniques are best suited to solve a particular drug design problem (e.g. how would you proceed if you need to develop an assay to identify molecules that prevent apoptosis). Of course, understanding a topic requires good knowledge of the material. However, you are not required to memorize specific drug structures, names or mathematical formulas. In general, my exams tend to be of problem-solving type. You may want to check out sample questions with answers from a previous exam. I believe that the following resources help you best in preparing for the exam: a) Lecture material. Was there anything that I said and was not clear? If so, please see if you can get answers by (i) listening to old course audio, (ii) asking me or (iii) reading the textbook/literature/Internet. b) Textbook provides a nice coverage on enzymes, receptors, and lead modification principles. It provides some background on computer modeling. One of the strengths of the textbook are a number of examples that are worked out in great detail. I did not cover these examples explicitly but they are good illustrations of concepts that I talked. The textbook also has a good number of end-of-chapter practice problems. I like some of them so much that I consider adopting them for the exam. c) Required reading. I know there is lots of it. First, make sure that you have some idea what is the main point of each of these papers. Then see if which papers you need to read more thoroughly to strengthen your understanding of the material. Please review the midterm study guide for earlier topics. The new topics that I consider most important for the final are: 1. Mechanisms of enzyme action • Biological reasons for enzyme catalysis • Transition state stabilization concept • Acid-base catalysis • Covalent catalysis • Proximity and role of entropy in catalysis 2. Molecular mechanism of enzyme targets that we discussed • Thymidylate synthetase • DNA methyltransferase • OMP decarboxylase • Hypoxanthine guanine phosphoribosyl transferase 3. Kinetics as a tool so study enzymes • What are kinetic studies good for • Practical aspects of kinetic measurements • Kinetic mechanisms • Enzyme inhibition models • Enzyme inactivation4. Enzyme inhibition • Why to inhibit enzyme • Transition state analogs as inhibitors • Role of kinetic isotope effects in determining transition state structures 5. Membrane receptor studies • Why to design ligands for membrane receptors • Binding studies: practical considerations • Displacement assays: principles • Prediction of receptor structures 6. Assay development • How to develop an assay: general considerations • Biochemical assays • Cell-based assays 7. Intermolecular interactions • Interactions in the gas phase • Charge-charge and charge dipole interactions • Polarizability and van der Waals forces • Relationships between free energy, entropy, enthalpy, energy • Hydrophobic effect • Conformational entropy considerations in binding 8. Structure-based drug design • Promises and problems of SBDD • The general process of SBDD • Visualization-based rational lead optimization • What can be computed about drugs • Quantum mechanics vs. molecular mechanics model • Docking as lead discovery / optimization approach • Free energy perturbation and thermodynamic cycles • Linear Interaction