Simulation of folding pathway studies of trp-cage miniprotein, amyloid A4 peptide, and a-conotoxin RgIA peptide

Protein is a sequence of a linear chain of amino acids. Protein folding is a physical process by which the linear chains of amino acid fold into its functional tertiary structures. Misfolding of a protein will lead to the problem such as diseases (cancer and influenza) in protein function. Discovery of protein folding will help the biologist to find the cause of misfolding and also assist the drug designer to find the cure for related diseases. Therefore the objective of this study is to investigate the folding pathways of Trp-cage miniprotein, Amyloid A4 peptide, and a-conotoxin RgIA. The folding process was simulated using molecular dynamics (MD) simulation in both explicit and implicit solvent. Amyloid A4 peptide (350ns) and a-conotoxin (800ns) were simulated in implicit solvent, while the simulation for Trp-cage (150ns) and a-conotoxin (200ns) were performed in explicit solvent method. The simulations produced a huge number of trajectories which were further analysed based on their root mean squared deviation (RMSD) values. The RMSD values showed that these trajectories approaching their simulated native structure (NMRMD). Besides that, a few crucial formations of hydrogen bond, disulfide bond, and salt bridge were involved in stabilizing the folding process. The best structure was identified by clustering all the trajectories based on RMSD, solvent accessible surface area (SASA), van der Waals interaction, electrostatic interactions and total energy of each trajectory. The best structure for Trp-cage miniprotein, Amyloid A4 peptide, a-conotoxin with implicit solvent and, a-conotoxin with explicit solvent were extracted at 79.76 ns, 224.85 ns, 184.20, and 104.20 ns, respectively