|Ph.D Student||Moskovitz Yevgeny|
|Subject||Monte Carlo Simulations of Proteins Adsorption onto|
|Department||Department of Chemical Engineering||Supervisor||Professor Simcha Srebnik|
|Full Thesis text|
This research examines denaturation following adsorption of proteins on untreated hydrophobic surfaces. An off-lattice Monte Carlo algorithm is used based on a previous model which considered perturbation of the intramolecular coordinates of the protein. The algorithm was implemented on a powerful multiprocessor cluster in message passing interface (MPI) code. The knowledge-based intra-molecular potential known as Miyazawa-Jernigan (MJ) was used to describe short- and long-ranged intramolecular interactions. The surface is described with two types of potentials: exponential decay and integrated Lennard-Jones. Different hydrophobic scales are used to describe the hydrophobic surface. The MJ potential is checked for preservation of native bulk conformations prior to protein adsorption. The following proteins are chosen for our analysis: lysozyme (PDB code - 1JSF) for its prevalence of α-helices, fibronectin (1FBR) for its prevalence of β-sheets, and a short single helix-containing peptide (1MEQ). The initial adsorption is examined using a large number of independent simulations, considering average energy values and their variances. Spatial dimensions of proteins are measured as radii of gyration and their components (perpendicular and parallel projection relative to the surface). In addition, protein structures are analyzed with detailed contact maps. Various optimization procedures are applied to the adsorption process. Tsallis generalized annealing and classic annealing are compared at normal conditions. The phenomenon of thermal stabilization of adsorbed proteins is characterized and thermal limits of denaturation of bulk and adsorbed conformations are established. The phenomenon of conformational freezing during annealing procedure is characterized. Freezing is found to be a function of strength of surface interactions and type of the potential, i.e., exponential decay leads to a higher probability of freezing. Different annealing schedules were designed with various temperature maxima and rate of cooling. The adsorbed conformations at the final annealing stages were examined with pseudo Ramachandran plots, which are used to follow the spreading of α-helixes and variation of β-sheets during adsorption. The makeup of the external adsorbed layer (0.5-1 nm thickness) is compared with reported ToF-SIMS measurements of fibronectin and lysozyme. When the adsorption process is managed by BULDG hydrophobic scale as a part of the integrated Lennard-Jones potential, there is a similarity to experimental data. Its high amphipathic index indicates similarity between intermediate folding stages and advanced stages of adsorption.