Interaction Between the Guanine Amino Group and the Adenine Six Membered Ring Stabilizes the Unusual Conformation of the CpA Step in B-DNA

Abstract

The CpA step is dramatically overwound in several B-DNA oligonucleotide crystal structures and its AT pair is substantially shifted towards the cytosine of the preceding base pair and towards the minor groove. We show using a geometrical analysis of the crystal data and empirical potential calculations that a strong interaction between the guanine amino group and the adenine six membered ring is responsible for the unique conformational properties of the CpA step.     

DNA Modeller: an interactive program for modelling stacks of DNA base pairs on a microcomputer

DNA Modeller is a microcomputer program for interactively manipulatingup to 20 bp in a DNA double helical arrangement. It calculatesthe van der Waals and electrostatic energies of base-base interactionsusing the AMBER potential, minimizes the energy with respectto the pair (buckle, propeller, opening, shear, stretch, stagger)and step (tilt, roll, twist, shift, slide, rise) parameters,calculates lengths of the canonical hydrogen bonds between thecomplementary bases, and calculates interatomic distances betweenthe successive base pairs. Input/output files are simple listsof the step and pair parameters or lists of the atom specifications(N1, C2, etc.) and their Cartesian coordinates (compatible withthe Desktop Molecular Modeller ^*.mol files). The program issupplied with a readbrk utility which transforms PDB/NDB tothe^*.mol format readable by DNA Modeller. The DNA crystal structuresdeposited in the PDB or NDB databases can thus be analyzed,and their bases visualized and interactively manipulated. Inaddition, DNA Modeller can calculate the base pair and stepgeometrical parameters and interaction energies. A plotter utilitycreates wire mono or stereo pictures of the bases. This programis designed for IBM-compatible computers working under DOS orcan run as a DOS application under MS Windows 3.x or Merge (SCOUnix DOS emulator).     

iGNM: a database of protein functional motions based on Gaussian Network Model

MOTIVATION: The knowledge of protein structure is not sufficient for understanding and controlling its function. Function is a dynamic property. Although protein structural information has been rapidly accumulating in databases, little effort has been invested to date toward systematically characterizing protein dynamics. The recent success of analytical methods based on elastic network models, and in particular the Gaussian Network Model (GNM), permits us to perform a high-throughput analysis of the collective dynamics of proteins. RESULTS: We computed the GNM dynamics for 20 058 structures from the Protein Data Bank, and generated information on the equilibrium dynamics at the level of individual residues. The results are stored on a web-based system called iGNM and configured so as to permit the users to visualize or download the results through a standard web browser using a simple search engine. Static and animated images for describing the conformational mobility of proteins over a broad range of normal modes are accessible, along with an online calculation engine available for newly deposited structures. A case study of the dynamics of 20 non-homologous hydrolases is presented to illustrate the utility of the iGNM database for identifying key residues that control the cooperative motions and revealing the connection between collective dynamics and catalytic activity.     

Mutual backbone phosphate group interactions promote DNA double helix bending at high salt concentrations in solution

Results of free energy calculations connected with the backbone phosphate group interactions upon local bending and helical twist modifications of A-, B- or Z-DNA at high salt concentrations have been reported recently (Jursa and Kypr 1990). Here we calculate energies necessary for DNA bending, using three models based on experimentally determined persistence length values. A comparison of energies following from the two quite different approaches suggests that high salt concentrations induce A- and mainly B-DNA bending into the double helix minor groove at least up to 10 degrees.     

Propeller-twisted adenine.thymine and guanine.cytosine base pairs tend to buckle and stagger in opposite directions.

Base pairs are propeller-twisted, buckled and staggered in DNA fragment crystals. These deformations were analyzed with isolated Watson-Crick base pairs using empirical potentials and buckle was found to almost linearly correlate with propeller. Interestingly, the thymine.adenine pair favours negative buckling for propellers mostly observed in DNA crystals while positive buckling is preferred by the cytosine.guanine pair. The propeller also induces opposite staggers in the adenine.thymine and guanine.cytosine base pairs.     

TMpro web server and web service: transmembrane helix prediction through amino acid property analysis

TMpro is a transmembrane (TM) helix prediction algorithm that uses language processing methodology for TM segment identification. It is primarily based on the analysis of statistical distributions of properties of amino acids in transmembrane segments. This article describes the availability of TMpro on the internet via a web interface. The key features of the interface are: (i) output is generated in multiple formats including a user-interactive graphical chart which allows comparison of TMpro predicted segment locations with other labeled segments input by the user, such as predictions from other methods. (ii) Up to 5000 sequences can be submitted at a time for prediction. (iii) TMpro is available as a web server and is published as a web service so that the method can be accessed by users as well as other services depending on the need for data integration. Availability: http://linzer.blm.cs.cmu.edu/tmpro/ (web server and help), http://blm.sis.pitt.edu:8080/axis/services/TMProFetcherService (web service).     

Mutual interactions of the phosphate groups in locally deformed backbones of various DNA double helices at high salt concentrations

Changes in the free energy of mutual phosphate group interactions are calculated that accompany bending of the A-, B- and Z-DNA backbones in 0.7, 2.1 and 4.2 mol/l NaCl aqueous solutions. The bending is often found to be favoured in the direction of the double helix grooves; B-DNA prefers bending into the major groove while minor groove is the preferred bending direction of A-DNA in the presence of 0.7 mol/l NaCl. Interestingly, the preferences are reversed in 4.2 mol/l NaCl. Further stabilization of A-DNA and B-DNA backbones is achieved in some cases if bending is combined with suitable local double helix twist alterations. Bending tendencies of Z-DNA backbone are generally weaker and they decrease, in contrast to B-DNA and A-DNA, with the increasing ionic strength.