Molecular Dynamics Simulation of Force-Induced Protein Domain Unfolding

122 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1999.Force-induced protein domain unfolding has been studied by steered molecular dynamics simulations (SMD). Two pulling protocols were adopted in the simulation. SMD with constant velocity pulling protocol qualitatively reproduced atomic force microscopy (AFM) observation that immunoglobulin and fibronectin type III domains have strong resistance against stretching force. SMD also located the exact extension of the main resistance, i.e., the force peak observed in both FM and SMD. The simulation suggested this strong resistance originated from the backbone hydrogen bonds and predicted helical protein domains are not designed to resist strong stretching force. SMD simulations with constant force pulling protocol, combine with mean first passage time approach in barrier crossing event, were used to estimate correctly the height of the main potential barrier on the force-induced domain unfolding pathway. A new protein domain classification method based on backbone hydrogen bonds pattern has been proposed. This method can distinguish domain's resistance against stretching force. Predictions from this classification scheme has been confirmed by AFM experiment. Combining SMD with atomic force microscopy, we were able to discover a new component of elasticity of muscle protein titin. Also has been suggested from the SMD simulation is a molecular recognition switch, a novel signaling mechanism, in extracellular matrix protein fibronectin.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD