Bibliography
M. P. Allen and D. J. Tildesley, "Computer Simulations of Liquids", Clarendon, Oxford, 1989.
Cohen, N. C., ed., "Guidebook on Molecular Modelling in Drug Design", Academic, San Diego (1996).
J. P. Doucet and J. Weber, "Computer-aided Molecular Design: Theory and Applications", Academic, San Diego (1996), Chapter 6.
J. Goodfellow, "Molecular Dynamics: An Overview of Applications in Molecular Biology", CRC Press, Boca Raton (1990).
J. M. Haile, "Molecular Dynamics Simulation", Wiley-Interscience, New York (1992).
Leach, A. R., "Molecular Modelling Principles and Applications", Longman, London (1996).
J. A. McCammon and S. C. Harvey, "Dynamics of Proteins and Nucleic Acids", Cambridge, Cambridge (1987).
M. Karplus and G. A. Petsko, Nature 347, 631-639 (1990).
M. Marsili, "Computer Chemistry", CRC Press, Boca Raton (1990), Chapter 4.
D. C. Rapaport, "The Art of Molecular Dynamics Simulation", Cambridge, Cambridge (1995).
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WWW Materials
There will be many hits for the search term 'molecular dynamics'. Some of these provide information about software and techniques for doing MD simulations. Some sites also provide MPEG movies of molecular motions estimated by MD methods. Similarly a search using the term 'simulated annealing' will provide many hits that describe applications of these ideas in chemical systems and for process optimization in fields outside chemistry.
Some Exercises
There is a Dynamics Tutorial in the SYBYL tutorial manual (Chapter 7). You might try the following exercises to get some ideas about how the dynamics modules of SYBYL work.
1. Build dichloromethane with SYBYL (The fragment methane is available and this can be modified.) Click on COMPUTE -> DYNAMICS -> SET UP DYNAMICS. Click on MODIFY and set the snapshot time to 5 fs and the coupling parameter to 10 fs. Click on OK to close this menu, then click on OK to start the dynamics run. In a few minutes a dynamics simulation of CH2Cl2 will run in which the integration time step has been 1 fs, a set of coordinates has been stored every 5 fs, and a dynamics trajectory of 1000 fs has been stored to disk. To play back the trajectory click on ANALYZE -> DYNAMICS -> ANALYZE DYNAMICS -> REPLAY TRAJECTORY. An apparent program bug changes the colors of the atoms during the replay, but the nature of the molecular motions in this molecule are clear. Why is virtually all of the motion observed localized to the CH2 group?
2. Simulated annealing is a procedure built around molecular dynamics simulations that can overcome energy barriers to the global minimum conformational energy. Cycles of heating and cooling are done to help a structure over these energy barriers. Build chlorocyclohexane in the chair conformation but with the chlorine in an axial position. Minimize the conformational energy. You will likely observe that the program finds a minimum that is some kind of distorted chair conformation with the chlorine still in the (high energy) axial orientation. Click on COMPUTE -> DYNAMICS -> SET UP ANNEALING. Accept all of the default parameters and click on OK to run the simulated annealing module. You will note that the molecule gyrates wildly during the heating part of each cycle but then takes on a recognizable conformation during the cooling phases. Minimize the structure that remains at the end of the simulated annealing calculation. You will probably find that the structure now has the chlorine in the lower energy equatorial environment.
Report
In part one, why is virtually all of the motion observed localized to the CH2 group?
In part two, tabulate and compare the minimized energies of both the axial and equatorial conformers of chlorocyclohexane. Hint: you will need to minimize both structures. Why, when you minimize the axial chlorocyclohexane, did it not go to the lower energy equatorial conformer?