Molecular Modeling 1 Introduction to Computational Molecular Physics

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

Bibliography Christopher J. Cramer, Essentials of Computational Chemistry, 2 nd Ed. , John Wiley & Sons, Hoboken, NJ, 2004. Software Avogadro-1. 1. 1 public free TINKER Molecular Modeling Package – public free Guass. View/Gaussian

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.

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

Here’s your Boeing 777, now make me the next Prozac. Ashutosh Jogalekar, August 17, 2012 Scientific American http: //blogs. scientificamerican. com/the-curiouswavefunction/2012/08/17/heres-your-boeing-777 -now-make-me-the-nextprozac/ 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?

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

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%

Insulin

Insulin hexamer + Zn