Protein structure resources

Protein structure resources and databases (coordinates, models, classifications, representative and benchmark sets) on the WWW Major protein structure archives and structure coordinate resources ... 

A worldwide repository for the processing and distribution of three-dimensional biologic macromolecular structure data.) The Protein Kinase Resource http //pkr.sdsc.edu/html/index. shtml... 

Protein information resource (Barker et al., 1999) was established in 1984 by the National Biomedical Research Foundation (NBRF) as a successor to the original NBRF Protein Sequence Database, developed over 20 years by the late Margaret O. Dayhoff and published as the Atlas of Protein Sequence and Structure (Dayhoff et al., 1965 Dayhoff, 1979). Since 1988 the database has been maintained by PIR-Intemational, a collaboration between the NBRF, the Munich Information Center for Protein Sequences (MIPS), and the Japan International Protein Information Database (JIPID). 

Protein primary structure databases include the following ExPASy Molecular Biology Server (Swiss-Prot) expasy.ch/ Protein Information resources (PIR) pir.georgetown.edu Protein Research Foundation (PRF) prf.or.jp/en/os.html. 

While there are many resources available for obtaining protein structure relationships, there are comparatively few resources available for understanding binding site relationships. Sali and co-workers developed the first... 

Summary. We recently developed an all-atom free energy force field (PFFOl) for protein structure prediction with stochastic optimization methods. We demonstrated that PFFOl correctly predicts the native conformation of several proteins as the global optimum of the free energy surface. Here we review recent folding studies, which permitted the reproducible all-atom folding of the 20 amino-acid trp-cage protein, the 40-amino acid three-helix HIV accessory protein and the sixty amino acid bacterial ribosomal protein L20 with a variety of stochastic optimization methods. These results demonstrate that all-atom protein folding can be achieved with present day computational resources for proteins of moderate size. 

This review indicates that all-atom protein structure prediction with stochastic optimization methods becomes feasible with present-day computational resources. The fact that three proteins were reproducibly folded with different optimization methods to near-native conformation increases the confidence in the parameterization of our all-atom protein force field PFFOl. The... 

Our discussion of globular protein structure begins with the principles gleaned from the earliest protein structures to be elucidated. This is followed by a detailed description of protein substructure and comparative categorization. Such discussions are possible only because of the vast amount of information available over the Internet from resources such as the Protein Data Bank (PDB www.rcsb.org/pdb), an archive of experimentally determined three-dimensional structures of biological macromolecules. 

This resource is maintained by the Molecular Biology Notebook Online project. It provides a wealth of information on the most important aspects of molecular biology such as life, structure and components of the cell, chromosome and DNA structure, protein structure, and diversity. 

The Sequence Retrieval System (Etzold et ah, 1996) is a network browser for databases at EBI. The system allows users to retrieve, link, and access entries from all the interconnected resources such as nucleic acid, EST, protein sequence, protein pattern, protein structure, specialist/boutique, and/or bibliographic databases. The SRS is also a database browser of DDBJ, ExPASy, and a number of servers as the query system. The SRS can be accessed from EBI Tools server at http // www2.ebi.ac.uk/Tools/index.html or directly at http //srs6.ebi.ac.uk/. The SRS permits users to formulate queries across a range of different database types via a single interface in three different methods (Figure 3.4) ... 

There are different classes of protein sequence databases. Primary and secondary databases are used to address different aspects of sequence analysis. Composite databases amalgamate a variety of different primary sources to facilitate sequence searching efficiently. The primary structure (amino acid sequence) of a protein is stored in primary databases as linear alphabets that represent the constituent residues. The secondary structure of a protein corresponding to region of local regularity (e.g., a-helices, /1-strands, and turns), which in sequence alignments are often apparent as conserved motifs, is stored in secondary databases as patterns. The tertiary structure of a protein derived from the packing of its secondary structural elements which may form folds and domains is stored in structure databases as sets of atomic coordinates. Some of the most important protein sequence databases are PIR (Protein Information Resource), SWISS-PROT (at EBI and ExPASy), MIPS (Munich Information Center for Protein Sequences), JIPID (Japanese International Protein Sequence Database), and TrEMBL (at EBI). ... 

The Protein Information Resources (PIR) (Wu et al., 2002) of NBRF in collaboration with MIPS and JIPID produces the annotated protein sequence database in the PIR-MIPS International Protein Sequence Database (PSD). The PSD is a comprehensive annotated and nonredundant protein sequence database. Its annotation includes concurrent cross-references to other sequence, structure, genomic and citatation databases, as well as functional descriptions and structural features. The PIR-International database is accessible at the PIR site, http //pir, georgetown.edu, and at the MIPS site, http //www.mips.biochem.mpg.de. 

Computation proteome annotation is the process of proteome database mining, which includes structure/fold prediction and functionality assignment. Methodologies of secondary structure prediction and problems of protein folding are discussed. Approaches to identify functional sites are presented. Protein structure databases are surveyed. Secondary structure predictions and pattern/fold recognition of proteins using the Internet resources are described. 

As scientists and engineers, natural self-assembly processes represent a tremendous resource, which we can use to create our own miniature materials and devices. Our endeavors are informed by hundreds of years of curiosity-driven research interested in the natural world. Our toolbox is further expanded by modem synthetic chemistry which extends beyond the realm of natural molecules. We can also create artificial environments to control and direct assembly and use computer-based tools and simulations to model and predict self-assembly pathways and their resulting protein structures. Many researchers believe we can use these modern tools to simplify, improve, and refine assembly processes. We have much to do in order to reach this ambitious goal but the next 10 years are likely to be filled with exciting discoveries and advances as self-assembling polypeptide materials move from the laboratory to the clinic or the manufacturing assembly line. 

With the advances in experimental solid-state NMR and computational resources (both software and computing power), it is now possible to use both the experimental and computational results (sometimes in a complementary way) to study biologically important macromolecules such as proteins. The quantum-chemical computation (particularly by density functional theory) of NMR parameters in solids has found important application in protein structure determination.30-36 Tesche and Haeberlen37 calculated the proton chemical shift tensor of the methyl groups in dimethyl terephthalate and found the theoretical results were in good agreement with the multiple pulse experiment. 

A readily available and abundant resource for examples on how to engineer proteins is Nature itself. The mechanisms of natural protein evolution have repeatedly succeeded in adapting protein function to ever changing environments. Understanding the principles and motives whereby new protein structures and functions emerge can provide useful guidelines for protein engineering. This chapter is directed towards the mechanisms of natural protein evolution, their implications on structure and function, and their experimental implementation in vitro. 

In the case of E2 ubiquitin conjugating enzymes, the interaction properties of about 200 protein structures were compared [49]. The pairwise similarity matrix was visualized as a dendrogram and a kinemage projection to three-dimensional space (see www.ubiquitin-resource.org). The analysis revealed relations between functional groupings and electrostatic properties at specific parts of the protein structure. 

The computational studies on protein structures have been carried out from different perspectives in biology. These perspectives include 1) comparison of protein structures, 2) structural analysis, and 3) protein structure prediction. Table 1 lists the online resources that are providing such services. 

Table 1 Online resources for protein structure analysis and prediction...

The first resources for computer modeling of protein structure are the nucleic acid and protein sequence databases (see Table 6.1), curated by the European Molecular Biology Laboratory (EMBL) in Europe, the National Center for Biotechnology Information (GenBank at the NCBl) in the United States, and the DNA Database of Japan (DDBJ) in Japan. These databases are accessible via the Internet, and most likely one s own scientific institution maintains a local version, which is updated through CD-ROMs released quarterly. Perhaps the predominant protein sequence database is SWISS-PROT. - Others include the nonredundant protein sequence database (OWL) and the protein identification resource database (PIR). ... 

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