The Key Event in Force-Induced Unfolding of Titins Immunoglobulin Domains Export

@article{lu:00, abstract = {Steered molecular dynamics simulation of force-induced titin immunoglobulin domain I27 unfolding led to the discovery of a significant potential energy barrier at an extension of <14\r{A} on the unfolding pathway that protects the domain against stretching. Previous simulations showed that this barrier is due to the concurrent breaking of six interstrand hydrogen bonds (H-bonds) between ²-strands A2 and G that is preceded by the breaking of two to three hydrogen bonds between strands A and B, the latter leading to an unfolding intermediate. The simulation results are supported by \r{A}ngstrom-resolution atomic force microscopy data. Here we perform a structural and energetic analysis of the H-bonds breaking. It is confirmed that H-bonds between strands A and B break rapidly. However, the breaking of the H-bond between strands A2 and G needs to be assisted by fluctuations of water molecules. In nanosecond simulations, water molecules are found to repeatedly interact with the protein backbone atoms, weakening individual interstrand H-bonds until all six A2G H-bonds break simultaneously under the influence of external stretching forces. Only when those bonds are broken can the generic unfolding take place, which involves hydrophobic interactions of the protein core and exerts weaker resistance against stretching than the key event.}, author = {Lu, Hui and Schulten, Klaus}, citeulike-article-id = {6008537}, citeulike-linkout-0 = {http://www.cell.com/biophysj/abstract/S0006-3495(00)76273-4}, day = {1}, keywords = {md, proteins, titin, unfolding}, month = {July}, number = {1}, pages = {51--65}, posted-at = {2009-10-26 07:58:57}, priority = {2}, title = {The Key Event in Force-Induced Unfolding of Titins Immunoglobulin Domains}, url = {http://www.cell.com/biophysj/abstract/S0006-3495(00)76273-4}, volume = {79}, year = {2000} }

TY - JOUR ID - lu:00 L3 - citeulike-article-id:6008537 N2 - Steered molecular dynamics simulation of force-induced titin immunoglobulin domain I27 unfolding led to the discovery of a significant potential energy barrier at an extension of <14Å on the unfolding pathway that protects the domain against stretching. Previous simulations showed that this barrier is due to the concurrent breaking of six interstrand hydrogen bonds (H-bonds) between ²-strands A2 and G that is preceded by the breaking of two to three hydrogen bonds between strands A and B, the latter leading to an unfolding intermediate. The simulation results are supported by Ångstrom-resolution atomic force microscopy data. Here we perform a structural and energetic analysis of the H-bonds breaking. It is confirmed that H-bonds between strands A and B break rapidly. However, the breaking of the H-bond between strands A2 and G needs to be assisted by fluctuations of water molecules. In nanosecond simulations, water molecules are found to repeatedly interact with the protein backbone atoms, weakening individual interstrand H-bonds until all six A2G H-bonds break simultaneously under the influence of external stretching forces. Only when those bonds are broken can the generic unfolding take place, which involves hydrophobic interactions of the protein core and exerts weaker resistance against stretching than the key event. IS - 1 EP - 65 TI - The Key Event in Force-Induced Unfolding of Titins Immunoglobulin Domains VL - 79 SP - 51 KW - md KW - proteins KW - titin KW - unfolding AU - Lu, Hui AU - Schulten, Klaus PY - 2000/07/01/ UR - http://www.cell.com/biophysj/abstract/S0006-3495(00)76273-4 ER -