|M.Sc Student||Eddie Rossinsky|
|Subject||Monte Carlo Simulation of Protein Folding in the|
Presence of Residue-Specific Binding Sites
|Department||Department of Chemical Engineering||Supervisor||Professor Srebnik Simcha|
The focus of this thesis is to determine model sequences that are able to fold into a unique ground state conformation and to investigate the stability of a folded model protein in an imprinted pore or surface. For the simulation algorithm we used Ensemble Growth Monte Carlo (EGMC) and dynamic Monte Carlo (DMC). The model used in our study is three-dimentional hydrophobic-polar (HP) model. We focus on 48-mer chains made up of 4 hydrophobic and 44 polar residues.
The concept of molecular imprinting can be potentially valuable in many applications such as separation or stabilization of enzymes and other biomolecules. Additionally, binding sites can be used for assistance in the protein folding process. In this case, the process performed within a molecularly imprinted cavities is modeled as hard walls having sites that are attractive to specific polar residues on the surface of the folded chain. Using EGMC simulation we determine all sequences that are able to fold to a unique structure. We find that the folded conformation can be stabilized using a small number of carefully selected residue specific sites. On the other hand, a random selection of surface-bound residues may only slightly contribute toward stabilizing the folded conformation, and in some cases may hinder the folding of the chain.
DMC simulation was used for verification of the increased stability of the folded conformation over a free chain. A different trend of the equilibrium population of folded chains as a function of residue-external site interactions is predicted with the two simulation methods.