STUDY OF MECHANICAL STABILITY OF OUTER SURFACE PROTEIN A (OSPA) SUBSTRUCTURES INVESTIGATED BY STEERED MOLECULAR DYNAMICS (SMD)

• Main Author: NURGAMAN, YONAN
• Format: Final Project
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/35866
• Institution: Institut Teknologi Bandung

The purpose of this study is to investigate factors in the stability of Outer surface protein A (OspA) from the Lyme disease spirochete, Borrelia burgdorferi. OspA contains three readily identifiable parts, a N-terminal globular domain (strands 1-7), a C-terminal globular domain (strands 11-21 and the C-terminal ?-helix), and a non-globular single-layer ?-sheet (strands 8-10) that connects the two globular domains. The single-layer ?-sheet segment is exposed to the solvent on both faces of the sheet and thus it does not contain a hydrophobic core. Previous studies showed that the whole protein, including the single-layer ?-sheet, is highly rigid and the protein has a very unusual structure, and we expected that a mechanical unfolding study of OspA might provide new mechanistic knowledge of the force-induced unfolding of proteins in general. In the present study, we modeled such mechanical unfolding work of ?-sheet segment (strands 7-9), the single-layer ?-sheet (strands 8-10), and ?-sheet segment (strands 7-11) by using Steered Molecular Dynamics (SMD) approach. The results showed that mechanical stability of OspA substructures is determine by boundary effect and the F126 residue which is guessed to be the key factor in the mechanical stability of OspA. Mutation of F126 to A126 does not inducted local destabilisation of the central ?-sheet, but seems to induct other area outside the central ?-sheet OspA. This results is in agreement with previous study showed that the F126A mutation significantly reduced the unfolding free energy of the C-terminal folding unit.