Molecular Modeling

2. Molecular Modeling 1 . Introduction to Computational Molecular Physics 2. Molecular Mechanics 3. Conformation Searching 4. Molecular Orbital Methods 5. Additional Quantum-based Methods 6. Molecular Dynamics Methods 7. Applications of Computational Molecular Physics

3. Bibliography Christopher J. Cramer, Essentials of Computational Chemistry, 2nd Ed., John Wiley & Sons, Hoboken, NJ, 2004. Software Avogadro-1.1.1 public free TINKER Molecular Modeling Package – public free GuassView/Gaussian

4. Werner Heisenberg was once asked what questions he thought were worth asking God. He is said to have quipped, “I would ask God two questions: “Why quantum mechanics?” and “Why turbulence?” Computational fluid dynamics can simulate the airflow around this Space Shuttle Boeing 777 was the first aircraft completely designed on a computer in 1995 .

5. The cockpit of a Boeing 777, the first airplane to be designed entirely on a computer

6. Here’s your Boeing 777, now make me the next Prozac. Ashutosh Jogalekar, August 17, 2012 Scientific American http://blogs.scientificamerican.com/the-curious-wavefunction/2012/08/17/heres-your-boeing-777-now-make-me-the-next-prozac/ Amazing fact: more than fifteen years after we designed an airplane on a computer, we still face enormous challenges in designing a small molecule made out of only fifty or sixty atoms that will bind to a protein with high affinity, block its function and halt the progress of the disease which it causes.  Fifteen years later I find it both fascinating and disconcerting that we can routinely design airplanes, bridges and skyscrapers on a computer but are still light years behind when it comes to designing even “simple” drugs. The two problems would seem to be of a similar order. Why the difference?

7. Gleevec: the Breakthrough in Cancer Treatment Leslie A. Pray http://www.nature.com/scitable/topicpage/gleevec-the-breakthrough-in-cancer-treatment-565

8. 1960 Nowell and Hungerford Phyladelphia chromosome 1973 Janet Rowley 9 and 22 chromosomes 1983 Heisterkamp BCR ABL genes 1990 BCR-ABL fusion gene produces BCR-ABL tirosine kinase protein signaling molecule, triggers cells to divide  overproduction and accumulation of immature white blood cells  chronic myelogenous leukemia 1996 Druker drug: tirosine kinase inhibitor Without drug, 30% of patients with CML survived for even five years, with imatinib 89%

17. Insulin

22. Insulin hexamer + Zn