Protein Data Bank Files Research Articles

Ab initio study of preferential interactions between aromatic side chains

The study of the tryptophan–histidine adducts, derived from the crystal structures available in the Brookhaven Protein Data Bank (PDB), using as model systems indole and (δ) 5-methylimidazole [G. Alagona, C. Ghio, S. Monti, J. Phys. Chem. A, 102, 6152 (1998)], has been extended for three of them (1esaB, 1s01, and 1lla, named after the PDB file to which they belong) to also include ε and protonated 5-methylimidazole at the Hartree–Fock (HF) and the second-order Møller–Plesset (MP2) levels, employing the 6-31G* basis set with the d exponents reduced to 0.25, thus named 6-31G*(0.25), and the HF/6-31G* internal geometries of the isolated partners. For these arrangements having a shallow or even repulsive HF interaction energy, the counterpoise correction to the basis set superposition error was introduced both at the HF and MP2 levels, using the 6-31G*(0.25) basis set, to test the reliability of the results obtained along the whole approaching path. The position (either δ or ε) of the proton on 5-methylimidazole does not affect much the results when the aromatic rings are almost parallel or in a T-shaped imidazole-across arrangement: the MP2 energy gap between the two adducts (favoring 1s01ε and 1llaε) is about 1.5 and 0.9 kcal/mol, respectively, and becomes 1.2 and 0.7 kcal/mol when counterpoise (CP) corrected. On the contrary there is a sensitive stabilization of the adduct when the imidazole H points toward the indole ring π density (1esaBε is repulsive at the HF level, while 1esaBδ is favorable by 3.7 kcal/mol at the HF level and by 5.5 kcal/mol at the MP2 level, either CP corrected or not). The adducts involving 5-methylimidazolium are much more stable than those with 5-methylimidazole, due to the electrostatic effect of the cation, which considerably increases the interaction energies and shortens the separations. The effect produced on the complex energy and equilibrium distance by the presence of a set of polarization function on the hydrogens with either normal or reduced exponents [6-31G** and 6-31G**(0.25, 0.15) descriptions] was also considered. Preliminary results on the preferential stabilization produced by the protein partial charges are reported. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 73: 175–186, 1999

A consensus residue analysis of loop and helix-capping residues in four-alpha-helical-bundle proteins.

A statistical study was performed on a set of proteins which adopt the four-alpha-helical-bundle tertiary motif in order to determine amino acid occurrences at helix-capping and loop positions. Eight X-ray crystal structures from the Brookhaven Protein Data Bank (PDB) were examined and N", N', Ncap, Ccap, C' and C" residues were assigned. In addition, a set of 55 protein sequences for the analogous proteins from different strains and species was taken from the Protein Information Resource and Swiss-Prot databanks. The residues at the capping and loop positions in this expanded data set were deduced by aligning these sequences with those from the PDB files. Similar trends were observed in the two data sets. In general, polar residues were predominant in the loops, although aromatic residues were also fairly common. Glycine, a highly flexible residue with an excellent 'helix-breaking' ability, was very common at the Ccap, C' and C" residues. Proline, which can force sharp turns in the direction of a peptide backbone, was only common at the N" residue. Residues which can participate in the N-capping box motif were found with high frequency. Capping motifs at the helix C-termini (Schellman and alphaL motifs) were also somewhat common, while another helix N-terminal stabilizing motif, the hydrophobic stable, was not common. The data presented in this study should prove useful for applying the 'consensus residue' approach to the de novo design of loop regions in helical bundle proteins.

Rendering of ray-traced images of molecular models on personal computers

The rendering on personal computers of photorealistic images of molecular graphics models by means of available public-domain ray-tracer programs is addressed. A computer program that generates the script files needed for rendering high-quality images by one of the best known ray-tracers, POVRAY, is presented and its features discussed. The program, named MOL2POV, allows the easy selection of various molecular models (sticks only, balls&sticks, space-filling CPK models) including distinct definitions of molecular surfaces (van der Waals, solvent accessible). MOL2POV can read Brookhaven's Protein Data Bank (PDB format) file and its allows a number of options to colour the molecular graphics according to the information to be emphasized in the model. A selection of eight high-resolution ray-traced images for molecular systems ranging from a small polyatomic molecule with 20 atoms to a DNA/protein complex with near 2000 atoms are displayed.

The PDBFINDER database: a summary of PDB, DSSP and HSSP information with added value.

The Protein Data Bank currently contains more than 4700 protein coordinate sets. It is often desirable to make a selection from these files based on a criterion like R-factor, experimental method, length of the amino acid sequence, or the number of homologous sequences in SWISSPROT. Doing this using the distributed form of the Protein Data Bank can be a tedious task, because (1) this requires reading one file for every single entry, and (2) not all of the information is present in a consistent computer readable way in all of the entries. The PDBFINDER database provides an easy to interpret file containing summary information about all Protein Data Bank files. Summary information from the DSSP (Definition of Secondary Structure of Proteins) and HSSP (Homology derived Secondary Structure of Proteins) databases is also included. Furthermore, where essential data were missing from the Protein Data Bank file, this information has been retrieved from the original literature. The latest version of the PDBFINDER database can be downloaded by anonymous ftp from swift.embl-heidelberg.de, directory:/pdbfinder. E-mail address hooft@embl-heidelberg.de.

WPDB– PC Windows-based interrogation of macromolecular structure

WPDB version 2.0 is a Microsoft-Windows-based program for browsing and interrogating native and derived structural features of biological macromolecules using data obtained from the Protein Data Bank (PDB). Major features of WPDB are a 20-fold compression of PDB files and query and analysis tools. The latter permit the geometric and sequence properties of structures to be analyzed individually or through comparative analysis. The object-oriented software design provides a high level of interaction between display windows, which facilitates information discovery. Three examples are given to illustrate the capabilities of the software, namely: location of the distribution of the most hydrophobic residues in the acid proteases; exploration of the geometric features of a 4-helix bundle motif; and examination of the effect of antibody binding by comparison of a neuraminidase with a neuraminidase-antibody complex. Additional details are available to World Wide Web (WWW) users at the URL http://www.sdsc.edu/CCMS/ Packages/wpdb.html.

Annotating PDB files with scene information

We have implemented extensions to the Brookhaven Protein Data Bank (PDB) file format for incorporating scene information such as viewing parameters, additional molecular information (e.g., van der Waals radii and atom colors), and user-defined graphics. These extensions were made in conformance with the PDB standard and provide sufficient information to render the scene in various styles such as space-filling images and ribbon diagrams. For the past 5 years these extensions have been used in the MidasPlus molecular modeling system and have proved both powerful and sufficient for generating complex molecular images. We propose that the extensions to the PDB presented here be adopted by the molecular modeling community for incorporation into visualization programs.

1.6 Å structure of semisynthetic ribonuclease crystallized from aqueous ethanol. Comparison with crystals from salt solutions and with ribonuclease A from aqueous alcohol solutions

The non-covalent combination of residues 1-118 of RNase A with a synthetic 14-residue peptide containing residues 111-124 of the molecule forms a highly active semisynthetic enzyme, RNase 1-118:111-124. With this enzyme, the roles played by the six C-terminal residues in generating the catalytic efficiency and substrate specificity of RNase can be studied using chemically synthesized analogs. The structure of RNase 1-118:111-124 from 43% aqueous ethanol has been determined using molecular-replacement methods and refined to a crystallographic R-factor of 0.166 for all observed reflections in the range 7.0-1.6 A (Protein Data Bank file ISSC). The structure is compared with the 2.0 A structure of RNase A from 43% aqueous 2-methyl-2-propanol and with the 1.8 A structure of the semisynthetic enzyme obtained from crystals grown in concentrated salt solution. The structure of RNase 1-118:111-124 from aqueous ethanol is virtually identical to that of RNase A from aqueous 2-methyl-2-propanol. Half of the crystallographically bound water molecules are not coincident, however. The structure is somewhat less similar to that of RNase 1-118:111-124 from salt solutions, with a major difference being the positioning of active-site residue His119.

LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions.

The LIGPLOT program automatically generates schematic 2-D representations of protein-ligand complexes from standard Protein Data Bank file input. The output is a colour, or black-and-white, PostScript file giving a simple and informative representation of the intermolecular interactions and their strengths, including hydrogen bonds, hydrophobic interactions and atom accessibilities. The program is completely general for any ligand and can also be used to show other types of interaction in proteins and nucleic acids. It was designed to facilitate the rapid inspection of many enzyme complexes, but has found many other applications.

Reconstruction of symmetry-related molecules from protein data bank (PDB) files

Many natural proteins are active as multimers. Crystallographic protein databases, however, generally store only part of the native multimer, the asymmetric unit, along with symmetry information. As a result of inaccuracies in the data, it is not always possible to reconstruct the native multimer. Here, a set of methods is presented that are designed to cope with inconsistencies in symmetry information. Applications include the validation of Protein Data Bank entries and the automatic generation of symmetry contacts for inspection and analysis.

PdbMotif--a tool for the automatic identification and display of motifs in protein structures.

A program PdbMotif, which automatically identifies protein motifs in a protein data bank file and generates a script file which can be read directly by the molecular rendering program RasMol, is described. PdbMotif accepts the standard PROSITE pattern syntax and will scan the PROSITE pattern database or a set of user defined patterns. Any motifs detected are automatically highlighted in the RasMol image.

Design and application of PDBlib, a C++ macromolecular class library.

PDBlib is an extensible object-oriented class library written in C++ for representing the three-dimensional structure of biological macromolecules. The software design strategy, features of many of the 129 classes currently distributed with the library, and two sample applications which use the library are described. Version 1.0 of the library represents the structural features of proteins, DNA, RNA and complexes thereof, at a level of detail on a par with that which can be parsed from a Protein Data Bank (PDB) entry. However, the memory-resident representation of the macromolecule is independent of the PDB entry and can be obtained from other sources, e.g. relational and object-oriented databases. PDBlib classes are organized into four categories: (i) classes that model the macromolecule; (ii) classes that enhance the extensibility of the library; (iii) classes that provide navigation facilities of the object-oriented macromolecular structure representation; and (iv) a class that loads a PDB file into the memory-resident object-oriented representation. A number of general-purpose procedures that return features of this representation and that are relevant to all biological disciplines are included in (i). The library has been used to develop PDBtool, a prototype structure verification tool, and PDBview, a structure rendering tool that requires no specialized graphics hardware and software. Current work centers on making the macromolecular structures represented by PDBlib persistent using a commercial object-oriented database and providing an additional class library, MMQLlib, to query those structures.

Protein electrostatics on personal computers

A computer program for the IBM PC series allowing the simple treatment of protein electrostatics is presented. It is based on the Bond Increment method for the calculation of molecular electrostatic potentials and generates input from Protein Data Bank files. Calculated electrostatic potentials for small model molecules with and without the application of orthogonalized atomic hybrid orbitals are compared to ab initio ones obtained with the 4-31G basis set, and a fair linear correlation found between values from both calculations. Another test of the method is the estimation of binding energies between native and mutant trypsin and some tetrapeptide substrates. Our approximate binding energies show good correlation with experimental values and with values obtained from the protein dipoles langevin dipoles method. With an appropriate linear correction, the method outlined here calculates electrostatic potentials near proteins relatively close to the ab initio values, both at small and large distances from the molecule. This feature seems to make it superior to others making use of atomic monopoles in the calculation.

A crystallographic molecular lattice builder applied to model lipid bilayers

It is often desirable for noncrystallographers to generate graphical models of three-dimensional crystal structures based on published coordinates of the atoms that make up the crystallographic unit cells. This type of visualization is particularly important for small-molecule crystals, such as lipid crystals, where one may be interested in investigating interactions between the individual molecules in addition to their conformations. BILAYER BUILDER is a program that generates a portion of the entire crystal structure from the coordinates of the molecules in a single unit cell. It gives users of small desktop computers, such as the Apple Macintosh, the capability to generate and examine model crystal structures with a molecular graphics display program. BILAYER BUILDER stores the crystal coordinates in a Brookhaven Protein Data Bank file format for possible use in a variety of applications on many different computers. Initially, it was written for use with lipid crystals and bilayers but may be used for building an assortment of molecular crystals.

HAMOG: Molecular graphics program for chemistry 5 biochemistry 5 molecular biology and enzyme research

HAMOG is a computer graphics program written in C for personal computers. Clear menus and a contextsensitive help option make the program easy to operate for occasional users. HAMOG provides a flexible environment for displaying and manipulating molecules and molecular systems. Special functions allow the investigation of structure-activity relationships of biologically active molecules. These include the calculation of molecular electrostatic potentials and fields, the superposition of molecules and the calculation of steric accessibilities. The visualization and manipulation of protein structures immediately readable from the Brookhaven Protein Data Bank files are also possible using HAMOG. The construction of any peptide or protein structure is very simple.

PAP: a protein analysis package

A program package has been assembled for the analysis of protein coordinates which are in the Brookhaven Protein Data Bank (PDB) format. These programs can be used to make two types of φ–ψ plots: a Ramachandran-style scatter plot, and a plot of φ and ψ values as a function of the linear sequence. Programs are also available for the display of distance diagonal plots for proteins. Two protein structures can be compared and the resulting r.m.s. differences in the structures plotted as a function of sequence. Temperature factors can be analyzed and plotted as a function of the linear sequence. In addition, various utilities are supplied for splitting PDB files which contain multiple subunits into individual files and also for renumbering PDB files. A utility is also provided for converting Amber-style PDB files into standard PDB files. Priestle's program RIBBON [J. Appl. Cryst. (1988), 21, 572–576] has been converted to run in a stand-alone mode with interactive rotation of the three-dimensional ribbon picture. Programs are Silicon Graphics four-dimensional level and have been tested on 4D70/GT and personal Iris workstations, although programs which give Postscript output have been converted to run on Digital Equipment Corporation VAX computers and Sun workstations.

A low cost system for the graphical display of space-filling models of proteins

Abstract An inexpensive system for creating and displaying high resolution color images of space-filling models of proteins is described. The system software consists of two BASIC programs, CONVERT and MOLVIEW, which allow the user to create two-dimensional projections of space-filling models of protein molecules, using data contained in standard Protein Data Bank files. By modifying certain subroutines in the BASIC programs, the user can specify color highlightning to emphasize certain aspects of the molecule. The user can interactively specify the viewing angle or store displayed images on diskettes. The software can be implemented on any MS-DOS personal computer that supports color graphics and GW-BASIC.