Chapter 24 Approaches to Modeling and Property Prediction of Model Peptides
Downloaded by NORTH CAROLINA STATE UNIV on October 29, 2012 | http://pubs.acs.org Publication Date: December 3, 1993 | doi: 10.1021/bk-1994-0544.ch024
Ruth Pachter, Robert L. Crane, and W. Wade Adams Materials Directorate, Wright Laboratory, WL/MLPJ, Wright-Patterson AFB, OH 45433-7702
Molecular simulations that predict a 'spring-like' molecular mechanical response of alpha-helical biopolymers with a reinforcing intramolecular hydrogen bonding network are presented in this study. Mechanical properties of extended biopolymer strands based on naturally occurring amino acids, e.g., poly(L-Ala), and for comparison poly(L-Glu) and poly(Ala-Gly) versus synthetic PPTA containing an amide bond, are compared to those assuming alpha-helical structures. Thus, the pivotal role of such motifs in biological systems utilizing superior compressive mechanical properties, especially of silk, can be inferred. Research that is currently underway in our laboratory in the design of optoelectronic materials with unique nonlinear optical and mechanical properties, particularly biopolymers that may be based on silk-type model systems, is found to be advanced by molecular modeling and properties prediction. We are investigating the use of biopolymers in pursuing the objective of developing new materials (1) to overcome existing mechanical disadvantages, at least at the molecular level. For example, although high-performance 'rigid-rod' polymer fibers (2,3,4) demonstrate high tensile properties (5,6) that may enable their incorporation into aerospace structures, these materials show low compressive strength, and their failure mode has been confirmed (7,8). On the other hand, flexible arrangements of alpha-helical biopolymer motifs found in Nature have important mechanical functions, as shown by the structures found in keratin in hair, myosin and tropomyosin in muscle, epidermin in skin, and fibrin in blood clots, but mostly by the elasticity of spider silk, thus lending support to the notion of designing polypeptide structures that mimic Nature. In particular, the coiled coil super-structure of the myosin tail leads to a hierarchy of intra- and inter- reinforcing interactions to accomplish a highly ordered array of a thick filament that provides the means for mechanical function in muscle contraction (9). Similarly, membrane skeletons that consist of spectrin networks which enable erythrocytes to resist strong shearing forces in blood flow, are comprised of flexible triple-stranded alpha-helical coiled coils providing the underlying mechanical stability and resilience of the erythrocyte membrane (10), while other membrane skeletons in erythrocytes are also important in altering and stabilizing the shapes of various types of cells (11). Moreover, it is supposed that alpha-helical strands are acting as a rubbery reinforcement matrix to provide elasticity to spider silk (12,13), validated to This chapter not subject to U.S. copyright Published 1994 American Chemical Society In Silk Polymers; Kaplan, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1993.
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some extent by our experimental study of these fibers in compression (14) that indicate no 'kinking (7,15) failure. Thus, the design of new biopolymers based on silk-type model systems is of special interest since spider silk arrangements were found to be governed by the same principles that apply to synthetic materials. Furthermore, since the synthesis and characterization of new polymeric nonlinear optical materials are of increasing interest (16,17), especially photochrome polypeptides (18), we have been involved in a continuing research effort to study the conformational flexibility in these systems (19,20). In addition to designing these materials to have superior mechanical properties by mimicking spider-silk structures, it is important to understand the underlying effects of the chromophore on the resulting polypeptide response to enable the design of photoresponsive polypeptides with controlled behavior. For example, in the photomodulation of the helix/coil equilibrium of poly(spiro-L-glutamate), the light-adapted polymer exists in an alphahelical conformation with the photochromic side-chain in its spiropyran form, while during dark adaptation a slow helix-to-coil dark reaction occurs, as the chromophores convert to the merocyanine form. Molecular simulations were used to study the effects of the nonlinear optical moieties, e.g., spiropyran and merocyanine species, on the alpha-helical core of poly(spiropyran-L-glutamate) (19). To further discern these effects, the influence of the chromophore conformation on a model of poly(spiropyran-L-tyrosine) was evaluated (21), and also of amphiphatic coiled coils (22). Although methods for modeling conformation and dynamics of polypeptides of defined secondary structure, e.g., silk model peptides (23) has been reviewed (24), and the motions of an alpha-helical polypeptide were examined by molecular and harmonic dynamics (25), none were carried out on the conformational flexibility of photochromic polypeptides. In this study we describe briefly the information from molecular dynamics simulations of β-sheet type strands to mimic the spider dragline sequence, for an initial insight into the possible stability of such sequences. Computational chemistry has indeed become a valuable tool for analyzing the dynamics and structure of macromolecular systems, and also for the theoretical prediction of properties, e.g., the ultimate mechanical properties (26). Attempts to calculate moduli of polymers have been reported (27,28,29), but these methods rely on molecular mechanics empirical potential energy functions, while no molecular orbital calculations were reported. A series of such calculations, namely of 'rigid-rod' polymers (poly(/?ara-phenylene benzobisoxazole), poly(parû-phenylene benzobisthiazole), poly(pûra-phenylene benzobisimidazole) (30,31)), polyethylene (32,33), and of highly conjugated structures (poly(p
