Protein folding structure analysis

Histidine Hydrogen Exchange for Analysis of Protein Folding, Structure, and Function... 

Keywords, protein folding, tertiary structure, potential energy surface, global optimization, empirical potential, residue potential, surface potential, parameter estimation, density estimation, cluster analysis, quadratic programming... 

Protein Structure Prediction, Sequence Analysis and Protein Folding... 

Ithough knowledge-based potentials are most popular, it is also possible to use other types potential function. Some of these are more firmly rooted in the fundamental physics of iteratomic interactions whereas others do not necessarily have any physical interpretation all but are able to discriminate the correct fold from decoy structures. These decoy ructures are generated so as to satisfy the basic principles of protein structure such as a ose-packed, hydrophobic core [Park and Levitt 1996]. The fold library is also clearly nportant in threading. For practical purposes the library should obviously not be too irge, but it should be as representative of the different protein folds as possible. To erive a fold database one would typically first use a relatively fast sequence comparison lethod in conjunction with cluster analysis to identify families of homologues, which are ssumed to have the same fold. A sequence identity threshold of about 30% is commonly... 

RB Russell, GJ Barton. Structural features can be unconserved m proteins with similar folds. An analysis of side-chain to side-chain contacts secondary structure and accessibility. J Mol Biol 244 332-350, 1994. 

To conclude, although the models used in lattice simulations are very simplified, the results provide general information on possible protein folding scenarios, albeit not on the detailed behavior of specific proteins, which would require more complex models and more accurate potentials. The contribution made by these simulations is that they enable an analysis of the structures, energetics, and dynamics of folding reactions at a level of detail not accessible to experiment. 

Combined analysis of structural and genomic data will certainly get more importance in the near future. Protein folds can be analysed for whole genomes. 

Structural analysis of the two pectate lyases PelC and PelE (5, 6), demonstrated that these proteins fold in a large heHx of parallel P strands. A stack of asparagine residues parallel to the helix probably plays a role in the stabUity of this structure. Identification of the structurally conserved amino adds lead to a reaHgnment of the protein sequences (7). In addition to Erwinia extracellular pectate lyases, the multiple aHgnment indudes the Bacillus subtilis pectate lyase, Aspergillus tdger and E. carotovora pectin lyases and plant proteins. 

With the development of NMR-based experiments for studying folded proteins, structural analysis of denatured proteins entered a new phase (Wuthrich, 1994 Dobson et al., 1994 Shortle, 1996). Whereas other spectroscopies and hydrodynamic studies give data that correspond to a complex sum of the properties of all residues, NMR spectroscopy extracts information about individual residues. For the first time, local structural features could be directly inferred from the behavior of sets of residues along the sequence. 

Because protein ROA spectra contain bands characteristic of loops and turns in addition to bands characteristic of secondary structure, they should provide information on the overall three-dimensional solution structure. We are developing a pattern recognition program, based on principal component analysis (PCA), to identify protein folds from ROA spectral band patterns (Blanch etal., 2002b). The method is similar to one developed for the determination of the structure of proteins from VCD (Pancoska etal., 1991) and UVCD (Venyaminov and Yang, 1996) spectra, but is expected to provide enhanced discrimination between different structural types since protein ROA spectra contain many more structure-sensitive bands than do either VCD or UVCD. From the ROA spectral data, the PCA program calculates a set of subspectra that serve as basis functions, the algebraic combination of which with appropriate expansion coefficients can be used to reconstruct any member of the... 

Quantitative analysis of protein IR and VCD spectra in terms of the fractional components (FC) of their secondary structure has taken different approaches, as noted earlier. The FTIR approach of assigning frequencies to specific components can, in principle, identify amounts of unordered structure in a protein fold. The viability of this approach... 

Scheich, C., Leitner, D., Sievert, V. et al. (2004) Fast identification of folded human protein domains expressed in E. coli suitable for structural analysis. BMC Structural Biology, 4, 4. 

Koing, S. 2005. Functional protein analysis using mass spectrometry. Current Organic Chemistry 9(9), 875-887. Osguthorpe, D. 2000. Ab initio protein folding. Current Opinion in Structural Biology 10(2), 146-152. 

Amyloid fibrils form from a variety of native proteins with diverse sequences and folds. The classic method for the structural analysis of amyloid has been X-ray fiber diffraction amyloid fibrils exhibit a characteristic diffraction signature, called the cross-/) pattern. This cross-/ pattern suggested a repeating structure in which /1-sheets run parallel to the fiber axis with their constituent /1-strands perpendicular to that direction (Sunde and Blake, 1997). This diffraction signature pointed to an underlying common core molecular structure for the amyloid fibril that could accommodate diverse sequences and folds. A number of groups have proposed amyloid folds that are consistent with the experimental data and these can be linked to repeating /1-structured units. 

---