Molecular Dynamic Simulations Of Proteion Folding

Determining the process by which proteins fold into particular shapes, characteristic of their amino acid sequence, is commonly called"the protein folding problem", which is an important topics in structural biology. A protein folds spontaneously into a unique 3D structure under physiological conditions. In contrast, this structure can be easily broken under some artificial conditions. such as, high temperatures, low/high PH, high pressure, or presence of denaturants. Protein folding can go wrong for many reasons. Irreversibly misfolded protein form insoluble protein aggregates found in certain tissues that are characteristic of some diseases, such as Alzheimer's Disease. Pressure is becoming increasesingly popular as a tool for investigating protein unfolding.Molecular dynamics simulations, which make use of classical Newton mechanics to generate trajectories, are playing an ever-expanding role in in computational power and concomitant improvements in force fields. In particular, the contribution of such studies to protein folding is immense. In this thesis, we focus on the amyloidβ-peptide (Aβ), to characterze the structural changes in both Aβ40 and Aβ42 peptide monomers, we perform 6 independent long-time molecular dynamics(MD) simulations at variable pressure of 0.1Mpa, 200Mpa and 1000Mpa for totle of 360ns.In chapter one, it discusses the following three problems: (1) the composing and structure of protein, (2) the origin of protein folding, folding pathway, folding course and the thermodynamics hypothesis and dynamics hypothesis during folding, (3) the significance of protein folding with computer simulations .In chapter two, the molecular dynamics simulation software GROMOS and its stimulant principle are discussed. It comprises experiential force field and potential energy function, and SHAKE constraint. At last, Verlet leapfrog method of molecular simulation and energy minimum method such as steepest descents method and conjugate gradients method are analysised.In chapter three, the Alzheimer's Disease and the charaters of amyloidβ-peptide (Aβ) is introduced. In Chapter four and five, the pressure-induced structural changes of Aβ40 and Aβ42 are discussed. Afer downloading the 3-Dstructure of Aβ40 and Aβ42 from the Protein Data Bank, with GROMOS96 software package, we perform 6 independent long-time molecular dynamics (MD) simulations at variable pressure of 0.1Mpa, 200Mpa and 1000Mpa for total of 360ns at 300K In aqueous solution.And then, we discussed the structural changes under various pressure. The moderate pressure such as 200Mpa could accelerate the unfolding rate ofα-helix, while higer pressure such as 1000Mpa restrained its unfolding rate.And Aβ42 couldn't formβ-sheet, while Aβ40 could.