Helix nucleation

Hummer, G., Garcia, A. E., and Garde, S. (2001). Helix nucleation kinetics from molecular simulations in explicit solvent. Proteins Struct. Fund. Genet. 42, 77-84. 

Ackerman, M.S., Bhate, M., Shenoy, N., Beck, K., Ramshaw, JA.M. and Brodsky, B. (1999) Sequence dependence of the folding of collagen-like peptides - single amino acids affect the rate of triple-helix nucleation. Journal of Biobgical Chemistry 274, 7668-7673. 

Collagen-like Polyproline type II (A-y-Gly) repeat Helix nucleation followed by zippering fiber formation still a significant challenge Perpendicular... 

Helix induction can be augmented by mimicking natural mechanisms using a variety of synthetic expedients. In general, these approaches seek to either stabilize or mimic helix nucleation sites or to naturally or artificially secure side-chain linkages. In most cases, these transformations make use of additional synthetic procedures beyond standard peptide synthesis methodologies to juxtapose amino acids or essential elements thereof in a manner that mimics a protein helix. 

Helix initiation (represented by the helix nucleation parameter a) in a random coil conformation is the slowest and energetically least favored step, whereas subsequent growth of the helix nucleus (represented by the helix propagation factor, s) is rapid and relatively favored. 83 ... 

Noting that Pro often plays the role of helix initiator and is often found at the beginning of helices, Kemp and co-workers have designed a series of helix-nucleating templates based on constrained di-[122 124 or triprolines 125-128 8-10 (Scheme 3). These templates can be easily incorporated at the N-terminus of any sequence. 

Hydrogen Bond Mimic a-Helix Nucleation from the N-Tenninus... 

Scheme 10 An i <— i + 4 Hydrogen Bond is Replaced with the Hydrazone Link To Form an a-Helix Nucleation Site151...

To expand the utility of the hydrogen bond mimic, J (23) has been modified to allow for extension from the N-terminus of a hydrazone-linked cyclic peptide 148 This allows not only the use of the hydrogen bond mimic in preparing internal loops, but also the positioning of a helix nucleation site between two peptides to form supersecondary structures. To accomplish this, an a-amino group can be added to J to give J (26) (Scheme 14). Incorporation of linker J into a nucleation site using the procedure applied to 23 allows it to mimic an N-cap formed... 

Fig. 1.2.5. The helix nucleating properties of AcHel depend on the two conformational states of the N-terminal imide bond.

Furthemiore, a kinetics trace obtained at the hehx wavelength indicates that the helix is completely formed within the time resolution of the pH-jump measurement (100 ns) This result not only demonstrates the efficacy of the laser-induced pH-jump but also has important implications for the dynamics of helix formation. The polyglutamic acid refolds from a highly disordered state and hence must cross the helix nucleation barrier, which it does on a very short timescale (<100 ns). 

This strategy is expected to yield highly stable short helices based on the hypothesis that helix nucleation is an entropically and enthalpically disfavored process therefore, factors that stabilize the first turn of the helix should promote helix formation (Fig. 18). The Zimm-Bragg [127] and Lifson-Roig [128] models for helix-coil transition predict that nucleation of the helix in a random coil is the slowest step, and subsequent growth of the helix is rapid. The peptide is considered... 

The proper alignment of two or more hydrogen-bond acceptors is crucial for the design of a successful helix nucleation template (Fig. 29.18). Kemp and Curran restrained two proline rings with a thiamethylene bridge... 

Kemp, D.S., Allen, T.J. and Oslick, S.L. (1991) Development of a 3-state equilibrium model for the helix-nucleation template Ac-Helj-OH. In Smith, J.A. and Rivier, J.E. (eds). Proceedings of the 12th American Peptide Symposium, pp. 352-355. ESCOM, Leiden. 

The first equation of (10.156) ensures that a chain doesn t form helices by itself. The second equation is described by the weight 02 for the initiation (nucleation) of a double helix, i.e., the probability for an arbitrarily chosen pair of monomers on different chains to start winding. This is the counterpart of single-chain helix nucleation. The cooperativity parameter a is expected to be small, but <72 can be of order unity if there is no strict restriction on monomer conformation in starting chain winding. 

Oosawa emphasized the nucleation of the helix with n = 4 that appeared to best describe the experimental data for actin (cf. Section III.B). However, helix nucleation by critical nuclei having n smaller or larger than 4 is also described by Oosawa s theory. Recent work has considered the model with n = 2 for the G F transformation [44] (see also [41]). In fact, the scheme in Figure 7(b) has general validity for a host of nucleation processes in solution including, for instance, the nucleation of spherical micelles and their sphere to rod transition (cf. Section II.A.3) [13]. 

The fundamental parameters, namely a, the helix nucleation constant, AHq, the enthalpy change on helix formation, and s (0°C), the average helix propagation parameter at 0°C, were all determined by Scholtz et al. by fitting the theoretical transition curve to the experimental ones [72],... 

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