Protein Data Bank computational analysis

The Human Genome Project went three-dimensional in late 2000. Structural genomics efforts will determine the structures of thousands of new proteins over the next decade. These initiatives seek to streamline and automate every experimental and computational aspect of the structural determination pipeline, with most of the steps involved covered in previous chapters of this volume. At the end of the pipeline, an atomic model is built and iteratively refined to best fit the observed data. The final atomic model, after careful analysis, is deposited in the Protein Data Bank, or PDB (Berman et ah, 2000). About 25,000 unique protein sequences are currently in the PDB. High-throughput and conventional methods will dramatically increase this number and it is crucial that these new structures be of the highest quality (Chandonia and Brenner, 2006). 

Interpretation of results of these studies is still difficult. Results of two-hybrid methods become more useful if they can be coordinated with other approaches. For example, computational methods can predict interactions from genome sequences alone. 11/0 More than 45,000 interactions have been predicted among yeast proteins. Reliable identification of such motifs as DNA-binding domains and Ca2+- binding domains can complement two-hybrid analysis.11 The yeast genome is predicted to contain 162 coiled-coil sequences and at least 213 unique interactions between them.0 Examination of sequences of protein families in the Protein Data Bank (PDB) led to prediction of 8151 interactions of 664 types between protein families in yeast.P... 

For new or would-be users of models, I present in Chapter 11 an introduction to molecular modeling, demonstrating how modern graphics programs allow users to display and manipulate models and to perform powerful structure analysis, even on desktop computers. This chapter also provides information on how to use the World Wide Web to obtain graphics programs and learn how to use them. It also provides an introduction to the Protein Data Bank (PDB), a World Wide Web resource from which you can obtain most of the available macromolecular models. 

Fig. 3 Evaluation of structures from the Protein Data Bank to identify and assess helical interfaces in protein-protein (HIPP) interactions. The helical interfaces were segregated based on binding interfaces and computational alanine scanning mutagenesis analysis. AAGavg > 2 kcal/mol AAGavg = 1-2 kcal/mol (Reprinted with permission from Jochim and Arora [50], Copyright (2010) American Chemical Society)...

An important factor in the progress of bioinformatics has been the constant increase in computer speed and memory capacity of desktop computers and the increasing sophistication of data processing techniques. The computation power of common personal computers has increased within 12 years approximately 100-fold in processor speed, 250-fold in RAM memory space and 500-fold or more in hard disk space, while the price has nearly halved. This enables acquisition, transformation, visuahsation and interpretation of large amounts of data at a fraction of the cost compared to 12 years ago. Presently, bioanalytical databases are also growing quickly in size and many databases are directly accessible via the Internet One of the first chemical databases to be placed on the Internet was the Brookha-ven protein data bank, which contains very valuable three-dimensional structural data of proteins. The primary resource for proteomics is the ExPASy (Expert Protein Analysis System) database, which is dedicated to the analysis of protein sequences and structures and contains a rapidly growing index of 2D-gel electrophoresis maps. Some primary biomolecular database resources compiled from spectroscopic data are given in Tab. 14.1. 

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