The mechanism by which conformational changes, particularly folding and unfolding, occur in proteins and other biopolymers has been widely discussed in the literature. Molecular dynamics (MD) simulations of protein folding present a formidable challenge since these conformational changes occur on a time scale much longer than what can be afforded at the current level of computational technology. Transition state (TS) theory offers a more economic description of kinetic properties of a reaction system by relating them to the properties of the TS, or for flexible systems, the TS ensemble (TSE). The volumetric properties of TSE’s are expressed as the logarithmic pressure derivatives of the rate constants, known as activation volumes △V‡ = -RT(∂lnk/∂P)T. Experimental activation volumes are available for a number of protein systems1. According to TST, activation volumes can be identified as the difference in volume between the TSE and reactant species △V‡ = V‡ - VR. The concept of a volume profile △VMD(y), describing how the volume of a molecular system varies along its reaction coordinate y, is widely used in discussing the mechanisms of high pressure reactions. Volume profiles can be calculated theoretically using our recently developed method2 based on molecular dynamics (MD) simulations. If the position y‡ of the TSE along the reaction coordinate is unknown, it can be found by locating △V‡ on the MD-generated volume profile: △VMD(y‡) = △V‡. We illustrate this approach by its successful application to the unfolding of a model chain system. 1For example: J. Woenckhaus, et al., Biophys. J. 80, 1518 (2001). 2H. Wiebe, et al., J. Phys. Chem. C 116, 2240 (2012).

MD-generated volume profiles as a tool for probing transition states of conformational changes

249th National Meeting (2015)

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