Helix dynamics

M. Levitt, Cold Spring Harbor Symp. Quant. Biol., 47, 251 (1983). Computer Simulation of DNA Double-Helix Dynamics. 

Barbate G, Ikura M, Kay L E, Pastor R W and Bax A 1992 Backbone dynamics of calmodulin studied by N relaxation using inverse detected two-dimensional NMR spectroscopy the central helix is flexible S/oefrem/sf/ y 31 5269-78... 

H. Kovacs, A.E. Mark, J. Johansson, and W.F. van Gunsteren. The effect of environment on the stability of an integral membrane helix Molecular dynamics simulations of surfactant protein C in chloroform, methanol and water. J. Mol. Biol, 247 808-822, 1995. 

Example Molecular dynamics simulations of selected portions of proteins can demonstrate the motion of an amino acid sequence while fixing the terminal residues. These simulations can probe the motion of an alpha helix, keeping the ends restrained, as occurs n atiirally m transmembrane proteins. You can also investigate the conformations of loops with fixed endpoints. 

Zhang L and J Hermans 1994. 3io-Helix versus a-Helix A Molecular Dynamics Studv of Conformational Preferences of Aib and Alanine. Journal of the American Chemical Society 116 11915-11921. 

An important characteristic of biomolecular motion is that the different types of motion are interdependent and coupled to one another. For example, a large-scale dynamic transition cannot occur without involving several medium-scale motions, such as helix rearrangements. Medium-scale motions cannot occur without involving small-scale motions, such as side-chain movement. Finally, even side-chain motions cannot occur without the presence of the very fast atomic fluctuations, which can be viewed as the lubricant that enables the whole molecular construction to move. From the point of view of dynamic... 

Elber et al. [48] applied this method to explore the dynamics of the C-peptide in water with impressive results. More than 30 trajectories of C-peptide were generated, and the process of helix fonnation in water was examined. Remarkably, a time step of 500 ps was used, which allowed for the study of peptide folding on extended time scales. 

Key Words —Carbon, molecular dynamics, torus, helix, graphitic forms. 

The properties of optimized helical structures, which were derived from torus C54D and Cs7a, >yps (A), (proposed by Dunlap) and torus C ,o> Dpe (B), (proposed by us) by molecular dynamics were compared. (see Figs. 9 (a) and 10). (Although the torus Cs7f, is thermodynamically stable, helix 57 was found to be thermodynamically unstable 14]. Hereafter, we use helix C to denote a helix consisting of one torus (C ) in one pitch. 

Good semi-quantitative agreements are found in diffraction patterns and proposed models obtained by molecular-dynamics[14], because the results of the ex-periments[31-34] are consistent with the atomic models proposed by us[14]. However, in the present state of high-resolution electron microscopy, taking into account, moreover, the number of sheets and the complicated geometry of the helix, it seems unlikely to directly visualize the pentagon-hexagon pairs. 

Since these investigations could be carried out only in the crystalline state, the question of the dynamics of the triple-helix formation and of the correlation of its stability with the amino acid sequence could be answered only with the help of other methods working in solution. 

A peptoid pentamer of five poro-substituted (S)-N-(l-phenylethyl)glycine monomers, which exhibits the characteristic a-helix-like CD spectrum described above, was further analyzed by 2D-NMR [42]. Although this pentamer has a dynamic structure and adopts a family of conformations in methanol solution, 50-60% of the population exists as a right-handed helical conformer, containing all cis-amide bonds (in agreement with modeling studies [3]), with about three residues per turn and a pitch of 6 A. Minor families of conformational isomers arise from cis/trans-amide bond isomerization. Since many peptoid sequences with chiral aromatic side chains share similar CD characteristics with this helical pentamer, the type of CD spectrum described above can be considered to be indicative of the formation of this class of peptoid helix in general. 

The thermodynamic stability of the 3i4-hehx in addition to the requirements for 3i4-helix formation have been studied extensively by NMR spectroscopy, circular dichroism and molecular dynamics. 

Fig. 2.47 The (P)-2.5-helical structure of N.N -linked oligoureas as determined by NMR meaurements in pyridine-c/5. (A) Stereo-view along the helix axis of a low energy conformer of nonamer 178 generated by restrained molecular dynamics calculations. (Adapted from [274]). The helix is characterized by (i) a rigid +)-SYnclinal arrangement around the C(a)-...

The head-to-tail-coupling reactions described above are potentially useful in the design of dynamic combinatorial libraries. Features of these reactions include the rapid and reversible formation of carbon-carbon bonds, multifunctional ene-imine building blocks, and formation of stereo centers upon ene-imine linkage. Support for template-directed synthesis utilizing ene-imine building blocks is the formation of a poly ene-imine species that could recognize 3 -GGA-5 sequences of DNA.48 It is noteworthy that some polyene-imines are helical and could form a triple helix with DNA. 

In the x-ray structure of rhodopsin, an amphipathic helix runs parallel to the membrane from the intracellular end of TM-VII beneath the seven-helical bundle to the other side of TM-I and TM-II. At this point, one or more Cys residues are often found and are known to be subject to a dynamic posttranslational modification with palmitic acid residues. Like the phosphorylation event, the palmitoylation process appears to be dynamically regulated by receptor occupancy and is also involved in the desensitization phenomenon. The two posttranslational modifications can influence each other. For example, the conformational constraint induced by palmitoylation may alter the accessibility of certain phosphorylation sites. Like the phosphorylation process, the functional consequences of palmitoylation also appear to vary from receptor to receptor. 

Borjesson U, Hiinenberger PH (2004) pH-dependent stability of a decalysine a-helix studied by explicit-solvent molecular dynamics simulations at constant pH. J Phys ChemB 108 13551-13559. 

E Pefferkorn, A Schmitt, R Varoqui. Helix-coil transition of poly(a,L-glutamic acid) at an interface Correlation with static and dynamic membrane properties. Biopolymers 21 1451-1463, 1982. 

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