PDB

Figure C2.5.5. Native stmcture of acyl-coenzyme A binding protein (first NMR stmcture out of 29 deposited to PDB). The figure was created using RasMol 2.6 [8],...

As a template for an intermediate conformation of protein kinase, the crystal structure of the binary complex of cAPK with adenosine (Ibkx.pdb in the Protein Data Bank) was used. As templates for open conformations... 

Fig. 2. Conformational free energy of closed, intermediate and open protein kinase conformations. cAPK indicates the unbound form of cAMP-dependent protein kinase, cAPKiATP the binary complex of cAPK with ATP, cAPKiPKP the binary complex of cAPK with the peptide inhibitor PKI(5-24), and cAPK PKI ATP the ternary complex of cAPK with ATP and PKI(5-24). Shown are averaged values for the three crystal structures lATP.pdb, ICDKA.pdb, and ICDKB.pdb. All values have been normalized with respect to the free energy of the closed conformations.

Preparation of a Brookhaven Protein Data Bank (PDB)-formatted [10] file containing the coordinates and appropriate names of all atoms, including all polar and aromatic hydrogens. 

Table 2 shows the results of our preliminary calculations of the pKa of the Cys403 residue, for several different models of the enzyme, based on two structures available from the PDB. In the case of the YPT structure, a crystal water molecule is close to Cys403 and was included in some of the calculations as part of the protein (i.e. it was treated with the same internal dielectric as that of the protein). Simulations denoted as -I-H2O in Table 2, include a crystallographically resolved, buried water molecule, situated 3.2lA from... 

Abstract. A smooth empirical potential is constructed for use in off-lattice protein folding studies. Our potential is a function of the amino acid labels and of the distances between the Ca atoms of a protein. The potential is a sum of smooth surface potential terms that model solvent interactions and of pair potentials that are functions of a distance, with a smooth cutoff at 12 Angstrom. Techniques include the use of a fully automatic and reliable estimator for smooth densities, of cluster analysis to group together amino acid pairs with similar distance distributions, and of quadratic progrmnming to find appropriate weights with which the various terms enter the total potential. For nine small test proteins, the new potential has local minima within 1.3-4.7A of the PDB geometry, with one exception that has an error of S.SA. 

The results of the optimization for 9 small test proteins, both for the potential with constant weights 1 and with the optimized weights, are given in Table 1. The optimized weights lead to smaller errors the resulting potentials have minima within 1.3-4.7A of the PDB geometry, with one exception that has an error of 8.5A. 

At present, the data base used for the fit was not specially selected to avoid homologous proteins. Thus, a further improvement can be expected from using data for one of the specially prepared lists of PDB files (cf. Hobohm et al. [9]). We also expect further improvements from replacing the polynomial fits in the potential estimation procedure by piecewise cubic fits though at the moment it is not clear how to select the number of nodes needed to get a good but not overfitting approximation to the density. Finally, we are considering... 

Besides the MDL Molfile formal, other file formats are often used in chemistry SMILES has already been mentioned in Section 2.3.3. Another one, the PDB file format, is primarily used for storing 3D structure information on biological macromolecules such as proteins and polynucleotides (Tutorial, Section 2.9.7) [52, 53). GIF (Crystallographic Information File) [54, 55] is also a 3D structure information file format with more than three incompatible file versions and is used in crystallography. GIF should not be confused with the Chiron Interchange Formal, which is also extended with. cif. In spectroscopy, JCAMP is apphed as a spectroscopic exchange file format [56]. Here, two modifications can be... 

PDB file. pdb Protein Data Bank file format for 3D stmcture information on proteins and polynucleotides nmm.rcsb.org 53... 

In 1971 the Protein Data Bank - PDB [146] (see Section 5.8 for a complete story and description) - was established at Brookhaven National Laboratories - BNL -as an archive for biological macromolccular cr7stal structures. This database moved in 1998 to the Research Collaboratory for Structural Bioinformatics -RCSB. A key component in the creation of such a public archive of information was the development of a method for effreient and uniform capture and curation of the data [147], The result of the effort was the PDB file format [53], which evolved over time through several different and non-uniform versions. Nevertheless, the PDB file format has become the standard representation for exchanging inacromolecular information derived from X-ray diffraction and NMR studies, primarily for proteins and nucleic acids. In 1998 the database was moved to the Research Collaboratory for Structural Bioinformatics - RCSB. 

An alternative and much more flexible approach is represented hy the STAR file format [L48, 149, which can be used for building self-describing data files. Additionally, special dictionaries can be constructed, which specify more precisely the contents of the eorresponding data files. The two most widely used such dictionaries (and file formats) arc the CIF (Crystallographic Information File) file format [150] - the International Union of Crystallography s standard for representation of small molecules - and mmCIF [151], which is intended as a replacement for the PDB format for the representation of macromolecular structures,... 

PDB files were designed for storage of crystal structures and related experimental information on biological macromolecules, primarily proteins, nucleic acids, and their complexes. Over the years the PDB file format was extended to handle results from other experimental (NM.R, cryoelectron microscopy) and theoretical methods... 

This rec ord/field terminology allows the treatment of a PDB file as an ordered collection of record types,... 

All the records defined for PDB files can be grouped into six categories on the basis of how many times a given record can appear in a PDB file and how many lines it may occupy. 

Each record in this category can appear only once in a PDB file and it occupies exactly one line. Examples of such records arc HEADER - the starting record of each PDB file discussed in detail below, END - the last (terminating) record, and CRYSTl - describing the crystallographic cell. 

All the records constituting a PDB file must appear in a strictly defined order, collected into sections, The order of the sections, together with a short description and sample record names, is presented in Thble 2-7 (source Ref. [33]). 

Having looked at the general structure of PDB files, let us now examine a sample PDB file. The file represents the structure of r conotoxin PNll polypeptide (PDB ID Ipcn) and was retrieved from the Protein Data Bank [53]. Figure 2-109 shows the 3D structure of the molecule. 

The molecule is built up of 1b amino acids, but the file also contains the positions of the oxygen atoms of 12 water molecules contained within the unit cell. To keep the example simple, only the most important parts of the file are presented and discussed here. Each part of the file is annotated with corresponding row and column numbers. The complete file can be obtained from the PDB [53] or from this book s website [153],... 

Representation of Chemico Compounds ll5 Table 2-7. Ordered list of sections in PDB files (souce Ref [53 ). 

The fir.-fit line of the file (see Figure 2-110) - the HEADER record - hold.s the moleculc. s classification string (columns 11-50), the deposition date (the date when the data were received by the PDB) in columns 51-59, and the PDB (Dcode for the molecule, which is unique within the Protein Data Bank, in columns 63-66. The second line - the TITLE record - contains the title of the experiment or the analysis that is represented in the entry. The subsequent records contain a more detailed description of the macromolecular content of the entiy (COMPND), the biological and/or chemical source ofeach biological molecule in the entiy (SOURCE), a set ofkeywords relevant to the entiy (KEYWDS). information about the experiment (EXPDTA), a list of people responsible for the contents of this entiy (.AUTHOR), a history of modifications made to this entiy since its release (REVDAT), and finally the primaiy literature citation that describes the experiment which resulted in the deposited dataset ()RNL). 

Figure 2-106. 3D molecular triJCtLjre of a-conoto in PNI1 polypeptide (PDB ID Ipen),... 

The REMARK 4-999 records contain other optional, but predefined, remarks, As shown above, the "REMARK 4 record specifies that the analyzed file conform fully with, the current (December 2002) version 2.2 of the PDB file format specification. 

Figure 2-112. Primary structure and heterogen sections of the analyzed PDB file.

As this short example shows. PDB files use different syntax for different records and both writing and reading such files require much effort. Another problem is the extensibility of this format to handle new kinds of information, which further complicates the file structure. The Protein Data Bank has been faced with the consequences - the existing legacy data comply with several different PDB formats, so they are not uniform and they arc more difEcuh to handle (145, 155, 157]. As mentioned in Section 2,9.7.1, there is a much more flexible and general way of representing molecular structure codes and associated information - the STAR file format and the file formats based on it. 

The Self-defining Text Archive and Retrieval (STAR) file format addresses primarily the problem of the inflexibility of the PDB file format, its fixed sets of allowable fields, and their strong dependence on order, To overcome the problems described, both the data. structure and the actual data items within a STAR file arc self-defined, which means that they are preceeded by corresponding names (labels) which identify and describe the data. The data may be of any type and there is no predefined order of the data. STAR files, in contrast to PDB files, are easy to read and write manually. The whole syntax of STAR files is very simple and is defined by only a few rules ... 

The most important feature of editing software is the option to save the structure in standard file formats which contain information about the structure (e,g., Mol-filc. PDB-filc). Most of these file formats arc ASCII text files (which can be viewed in simple text editors) and cover international standardized and normalized specifications of the molecule, such as atom and bond types or connectivities (CT) (see Section 2,4). Thus, with these files, the structure can be exchanged between different programs. Furthermore, they can seiwe as input files to other chemical software, e.g, to calculate 3D structures or molecular properties. 

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