@article {348, title = {A structure-based model fails to probe the mechanical unfolding pathways of the titin I27 domain}, journal = {The Journal of Chemical Physics}, volume = {139}, year = {2013}, pages = {065103}, publisher = {AIP}, abstract = {We discuss the use of a structure based Cα-Go model and Langevin dynamics to study in detail the mechanical properties and unfolding pathway of the titin I27 domain. We show that a simple Go-model does detect correctly the origin of the mechanical stability of this domain. The unfolding free energy landscape parameters xu and ΔG{\textdaggerdbl}, extracted from dependencies of unfolding forces on pulling speeds, are found to agree reasonably well with experiments. We predict that above v = 104 nm/s the additional force-induced intermediate state is populated at an end-to-end extension of about 75 {\r A}. The force-induced switch in the unfolding pathway occurs at the critical pulling speed vcrit ≈ 106{\textendash}107 nm/s. We argue that this critical pulling speed is an upper limit of the interval where Bell{\textquoteright}s theory works. However, our results suggest that the Go-model fails to reproduce the experimentally observed mechanical unfolding pathway properly, yielding an incomplete picture of the free energy landscape. Surprisingly, the experimentally observed intermediate state with the A strand detached is not populated in Go-model simulations over a wide range of pulling speeds. The discrepancy between simulation and experiment is clearly seen from the early stage of the unfolding process which shows the limitation of the Go model in reproducing unfolding pathways and deciphering the complete picture of the free energy landscape.}, keywords = {biochemistry, biomechanics, free energy, mechanical stability, molecular biophysics, molecular configurations}, doi = {10.1063/1.4817773}, url = {http://link.aip.org/link/?JCP/139/065103/1}, author = {Maksim Kouza and Chin-Kun Hu and Mai Suan Li and Andrzej Koli{\'n}ski} } @article {351, title = {Relationship between population of the fibril-prone conformation in the monomeric state and oligomer formation times of peptides: Insights from all-atom simulations}, journal = {The Journal of Chemical Physics}, volume = {132}, year = {2010}, pages = {165104}, publisher = {AIP}, abstract = {Despite much progress in understanding the aggregation process of biomolecules, the factors that govern its rates have not been fully understood. This problem is of particular importance since many conformational diseases such as Alzheimer, Parkinson, and type-II diabetes are associated with the protein oligomerization. Having performed all-atom simulations with explicit water and various force fields for two short peptides KFFE and NNQQ, we show that their oligomer formation times are strongly correlated with the population of the fibril-prone conformation in the monomeric state. The larger the population the faster the aggregation process. Our result not only suggests that this quantity plays a key role in the self-assembly of polypeptide chains but also opens a new way to understand the fibrillogenesis of biomolecules at the monomeric level. The nature of oligomer ordering of NNQQ is studied in detail.}, keywords = {aggregation, biochemistry, diseases, macromolecules, molecular biophysics, Proteins, self-assembly}, doi = {10.1063/1.3415372}, url = {http://link.aip.org/link/?JCP/132/165104/1}, author = {Hoang Bao Nam and Maksim Kouza and Hoang Zung and Mai Suan Li} } @article {353, title = {Dependence of protein mechanical unfolding pathways on pulling speeds}, journal = {The Journal of Chemical Physics}, volume = {130}, year = {2009}, pages = {145102}, publisher = {AIP}, keywords = {biochemistry, free energy, molecular biophysics, Proteins}, doi = {10.1063/1.3106761}, url = {http://link.aip.org/link/?JCP/130/145102/1}, author = {Mai Suan Li and Maksim Kouza} }