Protein structure prediction from amino acid sequences

There is a considerable impetus to predict accurately protein structures from sequence information because of the protein sequence/structure deficit as a consequence of the genome and full-length cDNA sequencing projects. The molecular mechanical (MM) approach to modeling of protein structures has been discussed in section 9.2, and the protein secondary structure prediction from sequence by statistical methods has been treated in section 9.5. The prediction of protein structure using bioinformatic resources will be described in this subsection. The approaches to protein structure predictions from amino acid sequences (Tsigelny, 2002 Webster, 2000) include ... 

Earlier structure predictions with coronins resulted in models of five-bladed P propellers, because only five WD repeats were recognised. However, many p propeller structures contain WD repeats with litde or no obvious sequence homology to the canonical sequence. Additionally, while typical WD repeats possess four to eight copies and up to 16 copies have been reported, almost all structures ofWD repeat proteins in the PDB contain seven blades per propeller. Keeping this in mind, more detailed analyses of coronins have been carried out and additional WD-like repeats were identified based on secondary structure prediction from amino acid sequences, indicating the presence of seven copies for coronins I(IA) - and 3 (IC) and 14 for coronin 7. The fold of a seven-bladed propeller was then confirmed by the crystal structure of a coronin 1 (lA) fragment. ... 

Eisenhaber, F Persson, B. Argos, P. (1995). Protein structure prediction recognition of primary, secondary, and tertiary structural features from amino acid sequence. Crit Rev Biochem Mol Biol 30,1-94. 

Marsden, R. L., L. J. McGuffin, and D. T. Jones. 2002. Rapid protein domain assignment from amino acid sequence using predicted secondary structure. Protein Sci 11 2814-24. 

This branch of bioinformatics is concerned with computational approaches to predict and analyse the spatial structure of proteins and nucleic acids. Whereas in many cases the primary sequence uniquely specifies the 3D structure, the specific rules are not well understood, and the protein folding problem remains largely unsolved. Some aspects of protein structure can already be predicted from amino acid content. Secondary structure can be deduced from the primary sequence with statistics or neural networks. When using a multiple sequence alignment, secondary structure can be predicted with an accuracy above 70%. 

The term "structural genomics" is used to describe how the primary sequence of amino acids in a protein relates to the function of that protein. Currently, the core of structural genomics is protein structure determination, primarily by X-ray crystallography, and the design of computer programs to predict protein fold structures for new proteins based on their amino acid sequences and structural principles derived from those proteins whose 3-dimensional structures have been determined. Plant natural product pathways are a unique source of information for the structural biologist in view of the almost endless catalytic diversity encountered in the various pathway enzymes, but based on a finite number of reaction types. Plants are combinatorial chemists par excellence, and understanding the principles that relate enzyme structure to function will open up unlimited possibilities for the... 

Gamier, J Gibrat, J. F. Robson, B. (1996). GOR method for predicting protein secondary structure from amino acid sequence. Methods Enzymol 266,540-53. 

Sternberg, M. J. E. and J. M. Thorton. 1978. Prediction of protein structure from amino acid sequence. Nature 271, 15-20. 

An acceptance of the basic principle that the amino acid sequence contains sufficient information to define the 3D structure of a protein in a particular environment has led to many diversified efforts to predict the conformation of proteins from amino acid sequences. Methods for abstracting biomacromolecnlar structures, in particular protein structnres (section 16.5), from their sequences can be aimed at the secondary structure, initially following three stages ... 

The statistical methods for predicting secondary structures of proteins from amino acid sequences are widely practiced among investigators in biochemistry and can be accessed at Network Protein Sequence Analysis (NPS ) via http //npsa-pbil.ibcp.fr... 

Once a successful set of rules for the folding of all a proteins is available, we can turn our attention to the known mainly a, a/jS and mainly p proteins and find, from a statistical analysis of their structures, which pairs of side chains destabilize helix-helix interactions and result in jS-sheet formation (previous investigations indicate that Phe-Phe, Phe-Tyr, Glu-Arg and Glu-Lys pairs are probable candidates for helix-helix destabilizers ). The rules thus derived from all the known protein structures can then be applied to the prediction of the three dimensional fold and packing of the secondary structures of other amino acid sequences whose structures are not known, that is, to the prediction of a cursory but full three-dimensional structure of a protein, which may be further refined by the application of standard potential energy functions. 

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