Polypeptide models

This chapter aims to summarize our efforts to investigate the effects of fluorinated amino acid substitutes on the interactions with natural protein environments. In addition to a rather specific example concerning the interactions of small peptides with a proteolytic enzyme, we present a simple polypeptide model that aids for a systematic investigation of the interaction pattern of amino acids that differ in side chain length as well as fluorine content within both a hydrophobic and hydrophilic protein environment. Amino acid side chain fluoiination highly affects polypeptide folding due to steric effects, polarization, and fluorous interactions. 

The stabihty of collagen is due to the formation of triple helixes, which is due to the presence of a Gly-Pro (OH)-Pro triplet. The influence of the replacement of 4-(R)-OH-Pro by 4-F-Pro on the stability of collagen has been the focus of studies on polypeptide models. These studies highlight the importance of stereoelectronic... 

Figure 4 CD Spectra of Polypeptide Models in the (3-Sheet Conformation1 -92-94-9513...

Numerous studies have been undertaken to elucidate the secondary structure of soluble elastin. These studies have been performed on elastin, elastin solubilized by oxalic acid (a-elastin) or potassium hydroxide (/, -elastin). synthetic polypeptide models of elastin, and tropoelastin. Techniques used include circular dichroism, FT-Raman, and electron microscopy. No consensus has been reached on the overall structure of elastin. 

The various aspects of our approach are demonstrated below within the context of a two-stranded coiled-coil polypeptide model that was designed to mimic the disulfide cross-linked two-stranded coiled-coil from the yeast transcription factor GCN4 [68-74] which was used by Hochstrasser and coworkers in their pioneering SM-FRET experiment. [30,33]... 

The plan of the remainder of this paper is as follows. Different ways of measuring conformational structure and dynamics via single-molecule FRET are described in Sec. 2 and demonstrated on the two-stranded coiled-coil polypeptide model in Sec. 3. The results are summarized and discussed in Sec. 4. 

Fig. 7 The correlation function (tiT2)d as obtained from kinetic Monte Carlo simulations for the polypeptide model (green). The normalized correlations functions (ki 2fc "2) (red) and (R1R2) (black) are also shown for the sake of comparison. All correlation function are normalized so that their initial value is equal to 1. The following parameters were used under different conditions (1) Folded state ko = = 2000,...

McCammon JA, Northrup SH, Karplus M, Levy RM (1980) Helix-coil transitions in a simple polypeptide model. Biopolymers 19 2033-2045... 

Osapay G, Taylor JW (1992) Multicyclic polypeptide model compounds.2. Synthesis and conformational properties of a highly a-helical uncosapeptide constrained by 3 side-chain to side-chain lactam bridges. J Am Chem Soc 114 6966-6973... 

J. McCammon, S. Northrup, M. Karplus, and R. Levy, Biopolymers, 19, 2033 (1980). Helix-Coil Transitions in a Simple Polypeptide Model. 

The broad aim of studying synthetic polypeptide model systems is to interpret better data obtained from studies of proteins and to design better experiments to gain new information about proteins. Protein studies using the polarization of fluorescence method have been reviewed recently by Weber (65), Steiner and Edelhoch (54) and Edelhoch and Steiner (16). 

The JW procedure was used in an ESMC simulation study of 38- and 54-residue (210) lattice polypeptide models [19,22] described above. Figure 5 shows the computed entropy function and its standard deviations obtained by the ESMC method with the JW procedure (including also the CBMC technique). The standard deviations of the computed entropy func-... 

Tozzini, V., Rocchia, W, and McCammon, J. A. [2006]. Mapping all-atom models onto one-bead coarse-grained models General properties and applications to a minimal polypeptide model,/. Chem. Theory Comput. 2, pp. 667-673. 

R.S. Bhatnagar, R.S. Rapaka, and D.W. Urry, Interaction of Polypeptide Models of Elastin with Prolyl Hydroxylase. FEBS Lett., 95, 61-64,1978. 

Fig. 8.4 Dependence of the computed average distance between the C -atoms as a function of Fq for the polypeptide model black circles), cystine (red circles), and DEDS (green circles) and obtained from force field equilibrium (at zero force) and force clamp MD (for Fq > OnN) simulations. Computational reference data for DEDS obtained from QM/MM simulations are shown by GEOMETRY FILE/created by CPMD brown triangles and the experimental reference based on the strained macrocycle [43] is marked by a violet square. The horizontal blue, pink and orange dotted lines are the average C -C distances of disulfide bonds in TDi, DO and interchain Ig proteins, respectively, whereas the cyan dotted line corresponds to intrachain Ig proteins. Reprinted from Ref. [42]...

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