Elasticity of Proteins and Polymers from Molecular Dynamics Simulations

Understanding the mechanical response of polymers to external force gives crucial insights into physiological processes. In this thesis we present the force extension relation of homo- and polypeptides as well as two synthetic polymer examples. Our findings rely on a combination of molecular or Brownian dynamics simulations, analytical modeling, and comparison to experimental results. First, we present the force−extension relations for the five homopeptides from molecular dynamics simulations in explicit water. The Kuhn length, equilibrium contour length and linear and nonlinear stretching moduli are deduced. An augmented freely rotating chain model, which accounts for side-chain interactions and restricted dihedral rotation, is shown to describe the simulated force−extension relations very well. We present a comparison between published experimental single-molecule force−extension curves for different polypeptides with simulation and model predictions. The simulations allow for the disentanglement of energetic and entropic contributions to the stretching energy of the polypeptides. Secondly, molecular dynamics simulations of a coiled coil linker present in photoreceptor histidine kinases are evaluated in terms of three different mechanical modes which are candidates for signal transmission. The levels of the output signals of shift, splay, and twist on one end of the coiled coil linker are quantified as a function over a wide range of frequencies for the driving force input on the other end of the coiled coil linker by investigation of response functions. Thirdly, the opposite temperature dependence of polyethylene glycol and poly(N-isopropylacrylamide) is investigated from a basis of single molecule force spectroscopy and molecular dynamics simulations in explicit water. Energetic and entropic contributions are deduced from simulations and compared for PEG and PNiPAM. Hydration effects are shown to explain the different temperature dependent responses. Finally, the response of the glycoprotein von Willebrand factor to linear shear flow is examined by a coarse-grained model in Brownian dynamics simulations including long range hydrodynamic interactions. Tensile forces and the shear-rate-dependent globular-coil transition are investigated. The scaling of the critical shear rate for the globular-coil transition with the monomer number is inverse for the grafted and non-grafted scenarios. This implicates that for the grafted scenario, larger chains have a decreased critical shear rate, while for the non-grafted scenario higher shear rates are needed to unfold larger chains