Mapping the energy landscape of tubulin under tension with molecular simulations

Microtubules (MTs) play major roles in the transport of organelles in the cell and in cell division. MTs are subject to permanent tension [1] and additional forces act on MTs when external mechanical perturbations are applied to cells. To elucidate the microscopic origins of the mechanical response in MTs, we have performed simulations of a self-organized polymer (SOP) model of tubulin, the building block of MTs. The SOP representation is an off-lattice minimalist description of a protein chain which allows us to perform force-induced unfolding simulations of large molecules at the loading rates and time scales of single-molecule experiments [2]. We show that the forced unfolding of tubulin involves a bifurcation in the unfolding pathways and map precise features of the complex energy landscape of tubulin by surveying the structures of the various metastable intermediates [3]. \\[0pt] References: \\[0pt] [1] Schek HT, Gardner MK, Cheng J, Odde DJ, Hunt AJ (2007) Curr Biol 17:1445--1455. \\[0pt] [2] Hyeon C, Dima RI, Thirumalai D (2006) Structure 14:1633--1645. \\[0pt] [3] Dima RI, Joshi H (2008) Proc. Natl. Acad. Sci. USA (accepted).