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Wilmon B. Chipman
Bridgewater State College
Bridgewater, MA 02325

Note: This article was scanned using OCR from the Spring 1994 CCCE Newsletter. Please contact us if you identify any OCR errors.
Molecular dynamics simulations are important tools for under standing the behavior of large biomolecules. I have adapted a molecular dynamics simulation of the denaturing of a protein alpha helix ( 1) for use in a senior biochemistry course for chemistry and biology majors. The exercise consists of five-parts:
1. Construction of a polyalanine alpha helix by template forcing.
2. Energy minimization of the alpha helix.
3. molecular dynamics simulation of denaturation.

4. examination of hydrogen bond lengths before, during and after the simulation.
5. viewing a "movie" of the denaturation.
A polymer of 15 alanine units was constructed by duplicating and connecting a minimized alanine structure found in a library of structures. Then a 15 amino acid alpha helix was "clipped" from cytochrome C for use as a template. By assigning constraints between corresponding atoms in the two polymers, the polyalanine polymer was forced to assume the conformation of the template alpha helix.
Then the template was removed., and an energy minimization was done on the polyalanine alpha helix. This adjusted the structure to a local energy minima for the actual methyl side chains. The use of an idealized alpha helix, with identical non-polar side chains, focuses the exercise on what happens to the hydrogen bonds between amides as the helix starts to denature.
Then the molecular dynamics simulation was run, using the Verlet algorithm. Since the actual simulation takes more than eight hours on a 386 PC with a floating point processor, the simulation was pre-run, and beginning, intermediate, and final structures were stored in a file library. The alpha helix was first heated to 1,000 C, and then allowed to denature. Structures from the simulation were saved at 2.5 picosecond iQtervals for a period of 305 picoseconds. During the simulation, hydrogen bonds lengthened, and broke, and sometimes reformed. (A total of 122 structures).
Selected files (wire frame models) were viewed to determine what happened to the length of the hydrogen bonds that hold the helix together as the simulation progressed. The hydrogen bond lengths can be color-coded (1.8- 1.9- is red, 1.9-2.0- is green, etc.) so that the changes in bond length are obvious.
Finally, a "movie" was constructed from all of the 122 structures that were saved from the simulation. (2) This "movie" may be stepped thru rapidly to provide an animated picture of the simulation. All of the individual structures may be examined. The animated version of the simulation destroys the student's picture of proteins as the rigid immobile structures that they see in text books.
1. HHoweler, U., MOBY 1.5: Molecular Modelling on the PC. Springer- Verlag, New York, 1993.
2. The construction of a movie cannot be done with version 1 .5 of MOBY .It requires version 1.6 which is currently in beta testing.


03/05/94 to 03/09/94