Free energies and forces in helix–coil transition of homopolypeptides under stretching

Abstract

We show here that constant velocity steered molecular dynamics (SMD) simulations of alpha-helices in a vacuum present a well defined plateau in the force-extension relationship for homopolypeptides having more than (approximately) twenty residues. With the processes being far away from equilibrium, the energies strongly depend on the stretching velocity. Importantly, for a given velocity variation, the energy variation depends also on the helix sequence. Additionally, our observations show that homopolypeptides made of ten different amino acids (Ala, Cys, Gln, Ile, Leu, Met, Phe, Ser, Thr and Val) present a linear helix-coil transition.

Two-phase stretching of molecular chains

“…The terminal regions of the chain are in a strongly stretched state, while the central region is stretched weakly [ Fig Thus, if the torsional rigidity is small enough, stretching of the α-helix proceeds via two-phase scenario with a typical plateau region where the tension remains constant. The scenario is confirmed by all-atom molecular dynamics simulations [22] and experiments [13,14]. The root cause of the non-uniform stretching in this case is the typical form of the hydrogen bond potential (4), which has an inflection point.…”

“…For example, forceextension plateau observed in single DNA molecule experiments (sometimes called the over-stretching plateau) is often explained by gradual un-zipping (force-induced melting) of the double helix in which Watson-Crick (WC) hydrogen bonds between base-pairs break [10][11][12][17][18][19], An alternative explanation involves cooperative transition of the whole structure into a new form called S-form where WC bonds remain intact [5,20], but the helix unwinds to form a straight ladder. In the case of polypeptides, force-extension plateau is attributed to alpha-helix unwinding [13,21,22]. Phenomenological descriptions based on various assumptions about stable monomer states were also proposed [23].…”

Evolution of Helical Mesostructures

“…This coiled structure can be topologically transformed from an internal helical structure (twisted rod), which is quite similar with the prevalent helix-coil transition model in polypeptides, [28][29][30][31] but much more complicated due to the hexagonal mesostructural symmetry and two helical operations (internal and external). This issue will be discussed later.…”

“…More importantly, we demonstrate a topological helix-coil transition model to successfully explain the structural evolution of different helical mesostructures. Although the helix-coil transition model has been applied in polypeptides to measure the molecule in an a-helix conformation versus a turn or random coil, [28][29][30][31] it is applied herein to a much more complicated mesostructure with not only two helical operations but also a 2D hexagonal packing symmetry. The boundary condition of the helix-coil transition is also clarified to explain in detail the formation of complex helical structures, such as the screwlike mesostructure.…”

Unfolding mechanism and free energy landscape of single, stable, alpha helices at low pull speeds

“…21,28 Force plateaus have also been seen in simulations and experiments of different molecules under tension and in a wide range of pulling velocities, suggesting two-state free energy landscapes associated with stretching are common to many (bio)polymers. For example, force plateaus have been observed in simulations of helices in tension, even at higher pulling velocities 16,18,35 or under adiabatic conditions; 34,36,37 in single molecule measurements of polylysine SAHs, 10 of helical segments connected by joints, 37,38 of coiled coils, 14,39 of dextran 19 and of double stranded DNA; 40,41 in steered molecular dynamics simulations of duplex DNA, 42 and simulations of coiled coils in tension 39 and shear. 43,44 The average plateau force (F p ; see Table 1), increases substantially with increasing pull speed, varying between F v¼10 À3 p ¼ ð87 AE 1Þ pN at the lowest pull speed up to E200 pN at the highest pull speed.…”