Avian pancreatic polypeptide

Example Crippen and Snow reported their success in developing a simplified potential for protein folding. In their model, single points represent amino acids. For the avian pancreatic polypeptide, the native structure is not at a potential minimum. However, a global search found that the most stable potential minimum had only a 1.8 Angstrom root-mean-square deviation from the native structure. 

Figure 30-5 Structure of the avian pancreatic polypeptide, a small globular protein. From Blundell et al.107...

Figure 40 Stereo view illustrating superposition of computed structure of avian pancreatic polypeptide (open circles)247 on the X-ray structure (solid circles).250 251 Only the Ca atoms are shown.

I. Glover, I. Haneef, J. Pitts, S. Wood, D. Moss, 1. Tickle, and T. Blundell, Biopolymers, 22, 293 (1983). Conformational Flexibility in a Small Globular Hormone X-ray Analysis of Avian Pancreatic Polypeptide at 0.98-A Resolution. 

In a controversial study, Sun [34] was able to use a GA to achieve surprisingly good predictions for very small proteins, like melittin, with 26 residues, and for avian pancreatic polypeptide inhibitor, with 36 residues. The algorithm involved a very complicated scheme and was able to achieve accuracy of less than 2 A versus the native conformation. However, careful analysis of this report suggests that the algorithm took advantage of the fact that the predicted proteins were actually included, in an indirect way, in the training phase that was used to parameterize the fitness function, and in a sense the GA procedure retrieved the known structure rather than predicted it. 

Fig. 2.80. A secondary structure of avian pancreatic polypeptide. (Reprinted from M. Irisa, T. Takahashi,...

A hybrid approach of the extended scaled particle theory (SPT) and the Poisson-Boltzmann (PB) equation for the solvation free energy of non-polar and polar solutes has been proposed by us. This new method is applied for the hydration free energy of the protein, avian pancreatic polypeptide (36 residues). The contributions form the cavity formation and the attractive interaction between the solute and the solvent to the solvation free energy compensate each other. The electrostatic conffibution is much larger than other terms in this hyelration free energy, because hydrophilic residues are ionized in water. This work is the first step toward further applications of our new method to free energy difference calculation appeared in the stability analysis of protein. 

Glover, I., Haneef, I., Pitts, J., Wood, S., Moss, D., Tickle, I., and Blundell, T. Conformational flexibility in a small globular hormone X-ray analysis of avian pancreatic polypeptide at 0.98-A resolution. Biopolymers 22, 293-304 (1983). 

Zhang H, Wong CF, Thacher T, Rabitz H. 1995. Parametric sensitivity analysis of avian pancreatic polypeptide (APP). Proteins Struct. Fund. Genet. 23 218... 

There are certain practical aspects that need to be taken into account in assessing the significance of temperature factors. Errors in measurement of intensities, arising for example from incomplete correction of radiation damage or absorption, will have more serious effects on temperature factors than on atomic positions. The data must extend to a resolution of better than 2 A, otherwise temperature factors tend to be underestimated. Restraints in the refinement which assume that positional disorders of bonded atoms are highly correlated may bias the results. However, it is encouraging that in several structures (e.g., rubredoxin [193] and avian pancreatic polypeptide [194]) where the restraints were relaxed these assumptions were found to be valid. 

Figure 11, Atomic positions and ellipsoids of anisotropic thermal vibrations for residues 7-10 of avian pancreatic polypeptide (from 1. Glover, Ph.D. Thesis, 1984, University of London, see [194]). The side chain of Tyr7 stacks above Gly9. There are indications of concerted thermal motion for these residues, with the largest vibrations in approximately the vertical direction of the page. There is least motion along the bond directions. Atoms at the end of side chains have greater anisotropic motion than main chain atoms.

Vincent SR, Johansson O, Hokfelt T, Skirboll L, Fide RP, Terenius L, Kimmel J, Goldstein M (1983a) NADPH-diaphorase a selective histochemical marker for striatal neurons containing both somatostatin-and avian pancreatic polypeptide (APP-) like immunoreactivity. J. Comp. Neurol., 217, 252-263. 

Albers, H.E., Ferris, C.F., Leeman, S.E. Goldman, B.D. (1984) Avian pancreatic polypeptide phase shifts hamster circadian rhythms when microinjected into the suprachiasmatic region. Science 223, 833-835. 

NPY is a member of the pancreatic polypeptide (PP) family of peptide hormones (Glover et al., 1985 Schwartz et al., 1990). A high-resolution X-ray analysis of one member of this family, avian pancreatic polypeptide (aPP), has been reported (Blundell et al., 1981 Glover et al., 1983), and a tertiary structure, referred to as the PP-fold (or the hair-pin loop), for the PP family was proposed. The PP-fold consists of... 

Plate 13 Computer-derived model of neuropeptide Y (NPY) based on the crystal structure of avian pancreatic polypeptide (aPP). For the detailed procedure used in generating this model, see Leban et al. (1995). 

Fig. 7.3. The PP fold protein structure found in avian pancreatic polypeptide (APP) and related peptides.

Adamo, M.L. Hazelwood, R.L. (1992). The effect of C-terminus and N-terminus iodination on avian pancreatic polypeptide (APP) binding to its chicken brain receptor. Neuropeptides, 21, 225-30. 

Hazelwood, R.L. (1993a). From avian pancreatic polypeptide to mammalian neuropeptides carbohydrate metabolism implications. In Avian Endocrinology, ed. P.J. Sharp, pp. 189-200. Bristol Society of Endocrinology. 

Inui, A., Okita, M., Miura, M. et al (1990). Characterization of the receptors for peptide-YY and avian pancreatic polypeptide in chicken and pig brains. Endocrinology, 127, 934-41. 

John, T.M., Pile, B., Hazelwood, R.L. George, J.C. (1989). Circulating levels of insulin and avian pancreatic polypeptide in pigeons under different experimental conditions. Gen. Comp. Endocrinol, 75, 71—7. 

The protein model on which the method is tested uses a three-atom per residue backbone and a one-atom side chain. " Optimization was carried out on melittin (26 residues), avian pancreatic polypeptide inhibitor (APPI) (36 residues), and apamin (18 residues). The fitness function used a molecular mechanics penalty as well as a penalty on the radius of gyration, which is a relatively straightforward value to obtain experimentally. In all three proteins, the GA found conformations of lower energy than that of the native structure, which was a problem with the force field, rather than with the optimization method. A standard SA method was also applied to this problem. It still found low-energy conformations, but took 100-200 times more function evaluations. 

An example employing a more realistic force field can also be found in the application of sensitivity analysis to study the determinants of the structural and thermodynamical properties of the protein avian pancreatic polypeptide (APP). It was found that the size and shape of the protein was determined to a large extent by electrostatic interactions, whereas the free energy of the protein was more sensitive to the surface-area-dependent solvation energy terms that modeled hydrophobic effects. Consequently, it is possible to develop an ad hoc force field that is designed to describe certain classes of (bio)molecular properties properly. The failure of such an ad hoc force field to describe properties of other types does not necessarily indicate that this force field is useless, rather, caution should be exercised in any attempt to apply it to other properties. 

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