Tertiary structure analysis

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

Cohen F E, M J E Sternberg and W R Taylor 1982 Analysis and Prediction of the Paclung oi. i-E a iinst a /3-Sheet in the Tertiary Structure of Globular Proteins. Journal of AdoljcuLir E 156 821-862. 

Cohen, F.E., Sternberg, M.J.E., Taylor, W.R, Analysis and prediction of the packing of a-helices against a p-sheet in the tertiary structure of globular proteins. 

These predictive methods are very useful in many contexts for example, in the design of novel polypeptides for the identification of possible antigenic epitopes, in the analysis of common motifs in sequences that direct proteins into specific organelles (for instance, mitochondria), and to provide starting models for tertiary structure predictions. 

However, 2D NOE studies are invaluable in structure determination, in particular of peptides and proteins here the NOEs give invaluable information for conformational analysis and the determination of the tertiary structures of proteins. 

Recently, there has been great interest in proteins that exhibit biological activity but lack a well-defined secondary or tertiary structure after purification (Dunker et al., 1998, 2001 Schweers et al., 1994 Uversky et al., 2000 Wright and Dyson, 1999). Such proteins are referred to as intrinsically disordered or unstructured. An analysis in 1998 of the Swiss Protein Database revealed that about 15,000 proteins in that database are likely to contain disordered segments at least 40 residues in length (Romero et al., 1998). Dyson and Wright (2002) review intrinsically disordered proteins in this volume. 

Initial classification of some cytokines was also undertaken on the basis of the specific biological activity by which the cytokine was first discovered (e.g. TNF exhibited cytotoxic effects on some cancer cell lines CSFs promoted the growth in vitro of various leukocytes in clumps or colonies). This, too, proved an unsatisfactory classification mechanism, as it was subsequently shown that most cytokines display a range of biological activities (e.g. the major biological function of TNF is believed to be as a regulator of both the immune and inflammatory response). More recently, primary sequence analysis of cytokines coupled to determination of secondary and tertiary structure reveal that most cytokines can be grouped into one of six families (Table 8.2). 

ExPASy Proteomics tools (http //expasy.org/tools/), tools and online programs for protein identification and characterization, similarity searches, pattern and profile searches, posttranslational modification prediction, topology prediction, primary structure analysis, or secondary and tertiary structure prediction. 

For molecular sizes that are amenable by NMR techniques, nucleic acids usually lack a tertiary fold. This fact, together with the characteristic low proton density, complicates NMR structural analysis of nucleic acids. As a result, local geometries and overall shapes of nucleic acids, whose structures have been determined by NMR, usually are poorly defined. Dipolar couplings provide the necessary long-range information to improve the quality of nucleic acid structures substantially [72]. Some examples can be found already in the literature where the successful application of dipolar couplings into structure calculation and structure refinement of DNA and RNA are reported [73-77]. 

The history of molecular biology has been a history of technological developments for determining the primary and tertiary structures of protein and nucleic acid molecules. Once the molecular structure is known, it provides clues to molecular functions. This is the principle of the structure-function relationship. Based on this principle the analysis of the amino acid sequence is performed to decipher the functional information from the sequence information. The analysis usually involves detection and prediction of empirical sequence—function relationships with additional consideration of known or predicted three-dimensional (3D) structures. Thus, the process can be represented schematically as ... 

Information concerning the tertiary structure of the proteins has been obtained from fluorometry, proton magnetic resonance spectroscopy, limited proteolysis, and X-ray analysis of protein crystals. 

Since the X-ray structural analysis of crystallized proteins yields the most direct information on the tertiary structure, many attempts have been made in the last decade to crystallize individual ribosomal proteins. However, it was many years before any progress in this field was made. The N- and C-terminal fragments of the . coU protein L7/L12 have been crystallized, and the crystals diffract to 4 and 2.6 A, respectively (Liljas et ai, 1978). According to the X-ray analysis, the C-terminal fragment (positions 53-120) has a compact, plum-shaped tertiary structure with three a helices and three p sheets (Leijonmarck et ai, 1980). 

From Sequence Analysis to the Modeling of the Chromatin Tertiary Structure Perspectives Acknowledgments References... 

VII. FROM SEQUENCE ANALYSIS TO THE MODELING OF THE CHROMATIN TERTIARY STRUCTURE... 

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