Date of Award

Summer 2012

Document Type


Degree Name

Master of Science (MS)


Chemistry & Biochemistry



Committee Director

Jennifer L. Poutsma

Committee Member

Lesley H. Greene

Committee Member

Patricia A. Pleban

Committee Member

Kenneth G. Brown

Call Number for Print

Special Collections LD4331.C45 T359 2012


For over five decades, different experiments have been performed to research how proteins attain their native three dimensional structures. However, the folding problem continues to be a puzzle in modern science. The design of two proteins that have maximal sequence identity but different folds and functions is one method that is being used to study the relationship between protein structure and amino acid sequence. In particular, mutant proteins of Streptococcus protein G, GA and GB, have 95% sequence identity and a 3a helix fold and β4/a fold, respectively. Molecular dynamics simulations of GA95 and GB95 at high temperatures were used to unfold the proteins and observe how the long range interactions between the amino acids change during the unfolding process. Comparison of the persistent interactions with the locations of the non-identical residues will provide further insight into how these amino acids encode the protein fold.

Three independent simulations of each protein were performed at 550 K. For each trajectory, the long range contact distances versus time were calculated. The most important long range interactions in maintaining the 3a-helical fold of GA95 are a1/ a2 and a2/a3 interactions, which include Alai 6-lle30, Ile17-1le30, Leu20-11e30, Tyr29- Leu45, Tyr29-lle49, and Ile33-Va142. Four of these interactions have one of the nonidentical residues, Leu20, Ile30, and Leu45. Residues 20 and 30 are found to be more important than residue 45 in GA95 because they form a strong long range interaction between a1 and a2 helices, which may explain their stability during the unfolding simulation.

In GB95, interactions between β1/β2, β3/β4, β1/a, and a/β4 are the most important ones in determining the β4+a fold. These include Thr1-Ala20, Tyr3-AIa20, Thr44-Thr53, Tyr45-Phe52, Va142-Thr55, Gly41-Thr55, Leu5-Phe30, Tyr3-Ala26, and Phe30-Phe52. Five interactions have one of the non-identical residues. Of all these interactions, the most important interaction is Tyr45-Phe52, which was observed to have a significant number of contacts at the end of the simulation. Hence, residue 45 is the most important non-identical residue in GB95.


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