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Bohdan Schneider

Publications and source records attributed to Bohdan Schneider.

11 recordsLinked to original sources
PubMed2006

Calculation of structural behavior of indirect NMR spin-spin couplings in the backbone of nucleic acids.

Calculated indirect NMR spin-spin coupling constants (J-couplings) between (31)P, (13)C, and (1)H nuclei were related to the backbone torsion angles of nucleic acids (NAs), and it was shown that J-couplings can facilitate accurate and reliable structural interpretation of NMR measurements and help to discriminate between their distinct conformational classes. A proposed stepwise procedure suggests assignment of the J-couplings to torsion angles from the sugar part to the phosphodiester link. Some J-couplings show multidimensional dependence on torsion angles, the most prominent of which is the effect of the sugar pucker. J-couplings were calculated in 16 distinct nucleic acid conformations, two principal double-helical DNAs, B- and A-, the main RNA form, A-RNA, as well as in 13 other RNA conformations. High-level quantum mechanics calculations used a baseless dinucleoside phosphate as a molecular model, and the effect of solvent was included. The predicted J-couplings correlate reliably with available experimental data from the literature.

Algorithms↗
PubMed2006

Indirect NMR spin-spin coupling constants 3J(P,C) and 2J(P,H) across the P-O...H-C link can be used for structure determination of nucleic acids.

Calculated indirect NMR spin-spin coupling constants (3)J(P,C) and (2)J(P,H) were correlated with the local structure of the P-O...H-C linkage between the nucleic acid (NA) backbone phosphate and the H-C group(s) of a nucleic acid base. The calculations were carried out for selected nucleotides from the large ribosomal subunit (Ban et al. Science 2000, 289, 905) with the aim of identifying NMR parameters suitable for detection of certain noncanonical RNA structures. As calculations in the model system, dimethyl-phosphate-guanine, suggest, the calculated indirect spin-spin couplings across the linkage are sensitive to the mutual orientation and distance between the phosphate and nucleic acid base. A short distance between the nucleic acid base and phosphate group and the angles C...P-O and P...C-H smaller than 50 degrees are prerequisites for a measurable spin-spin interaction of either coupling (|J| > 1 Hz). A less favorable arrangement of the P-O...H-C motif, e.g., in nucleotides of the canonical A-RNA, results in an effective dumping of both spin-spin interactions and insignificant values of the NMR coupling constants. The present work indicates that quantum chemical calculations of the indirect spin-spin couplings across the P-O...H-C motif can help detect some rare but important backbone topologies, as seen for example in the reverse kink-turn. Measuring of (3)J(P,C) and (2)J(P,H) couplings can therefore provide critical constraints on the NA base and phosphate geometry and help to determine the structure of NAs.

Carbon↗
PubMed2006

Cations and hydration in catalytic RNA: molecular dynamics of the hepatitis delta virus ribozyme.

The hepatitis delta virus (HDV) ribozyme is an RNA enzyme from the human pathogenic HDV. Cations play a crucial role in self-cleavage of the HDV ribozyme, by promoting both folding and chemistry. Experimental studies have revealed limited but intriguing details on the location and structural and catalytic functions of metal ions. Here, we analyze a total of approximately 200 ns of explicit-solvent molecular dynamics simulations to provide a complementary atomistic view of the binding of monovalent and divalent cations as well as water molecules to reaction precursor and product forms of the HDV ribozyme. Our simulations find that an Mg2+ cation binds stably, by both inner- and outer-sphere contacts, to the electronegative catalytic pocket of the reaction precursor, in a position to potentially support chemistry. In contrast, protonation of the catalytically involved C75 in the precursor or artificial placement of this Mg2+ into the product structure result in its swift expulsion from the active site. These findings are consistent with a concerted reaction mechanism in which C75 and hydrated Mg2+ act as general base and acid, respectively. Monovalent cations bind to the active site and elsewhere assisted by structurally bridging long-residency water molecules, but are generally delocalized.

Base Sequence↗
PubMed2005

Sugar pucker modulates the cross-correlated relaxation rates across the glycosidic bond in DNA.

The dependence of N1/9 and C1' chemical shielding (CS) tensors on the glycosidic bond orientation (chi) and sugar pucker (P) in the DNA nucleosides 2'-deoxyadenosine, 2'-deoxyguanosine, 2'-deoxycytidine, and 2'-deoxythymidine was studied using the calculation methods of quantum chemistry. The results indicate that these CS-tensors exhibit a significant degree of conformational dependence on chi and P structural parameters. The presented data test underlying assumptions of currently established methods for interpretation of cross-correlated relaxation rates between the N1/9 chemical shielding tensor and C1'-H1' dipole-dipole (Ravindranathan et al. J. Biomol. NMR 2003, 27, 365-75. Duchardt et al. J. Am. Chem. Soc. 2004, 126, 1962-70) and highlight possible limitations of these methods when applied to DNA.

Computer Simulation↗
PubMed2004

Knowledge-based elastic potentials for docking drugs or proteins with nucleic acids.

Elastic ellipsoidal functions defined by the observed hydration patterns around the DNA bases provide a new basis for measuring the recognition of ligands in the grooves of double-helical structures. Here a set of knowledge-based potentials suitable for quantitative description of such behavior is extracted from the observed positions of water molecules and amino acid atoms that form hydrogen bonds with the nitrogenous bases in high resolution crystal structures. Energies based on the displacement of hydrogen-bonding sites on drugs in DNA-crystal complexes relative to the preferred locations of water binding around the heterocyclic bases are low, pointing to the reliability of the potentials and the apparent displacement of water molecules by drug atoms in these structures. The validity of the energy functions has been further examined in a series of sequence substitution studies based on the structures of DNA bound to polyamides that have been designed to recognize the minor-groove edges of Watson-Crick basepairs. The higher energies of binding to incorrect sequences superimposed (without conformational adjustment or displacement of polyamide ligands) on observed high resolution structures confirm the hypothesis that the drug subunits associate with specific DNA bases. The knowledge-based functions also account satisfactorily for the measured free energies of DNA-polyamide association in solution and the observed sites of polyamide binding on nucleosomal DNA. The computations are generally consistent with mechanisms by which minor-groove binding ligands are thought to recognize DNA basepairs. The calculations suggest that the asymmetric distributions of hydrogen-bond-forming atoms on the minor-groove edge of the basepairs may underlie ligand discrimination of G.C from C.G pairs, in addition to the commonly believed role of steric hindrance. The analysis of polyamide-bound nucleosomal structures reveals other discrepancies in the expected chemical design, including unexpected contacts to DNA and modified basepair targets of some ligands. The ellipsoidal potentials thus appear promising as a mathematical tool for the study of drug- and protein-DNA interactions and for gaining new insights into DNA-binding mechanisms.

Algorithms↗
PubMed2004

RNA conformational classes.

RNA exhibits a large diversity of conformations. Three thousand nucleotides of 23S and 5S ribosomal RNA from a structure of the large ribosomal subunit were analyzed in order to classify their conformations. Fourier averaging of the six 3D distributions of torsion angles and analyses of the resulting pseudo electron maps, followed by clustering of the preferred combinations of torsion angles were performed on this dataset. Eighteen non-A-type conformations and 14 A-RNA related conformations were discovered and their torsion angles were determined; their Cartesian coordinates are available.

Models, Molecular↗
PubMed2002

The Protein Data Bank.

The Protein Data Bank [PDB; Berman, Westbrook et al. (2000), Nucleic Acids Res. 28, 235-242; http://www.pdb.org/] is the single worldwide archive of primary structural data of biological macromolecules. Many secondary sources of information are derived from PDB data. It is the starting point for studies in structural bioinformatics. This article describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information and plans for the future development of the resource. The reader should come away with an understanding of the scope of the PDB and what is provided by the resource.

Databases, Protein↗
PubMed2002

The Nucleic Acid Database.

The Nucleic Acid Database was established in 1991 as a resource to assemble and distribute structural information about nucleic acids. Over the years, the NDB has developed generalized software for processing, archiving, querying and distributing structural data for nucleic acid-containing structures. The architecture and capabilities of the Nucleic Acid Database, as well as some of the research enabled by this resource, are presented in this article.

Computer Graphics↗
PubMed2002

Protein and drug interactions in the minor groove of DNA.

Interactions between proteins, drugs, water and B-DNA minor groove have been analyzed in crystal structures of 60 protein-DNA and 14 drug-DNA complexes. It was found that only purine N3, pyrimidine O2, guanine N2 and deoxyribose O4' are involved in the interactions, and that contacts to N3 and O2 are most frequent and more polar than contacts to O4'. Many protein contacts are mediated by water, possibly to increase the DNA effective surface. Fewer water-mediated contacts are observed in drug complexes. The distributions of ligands around N3 are significantly more compact than around O2, and distributions of water molecules are the most compact. Distributions around O4' are more diffuse than for the base atoms but most distributions still have just one binding site. Ligands bind to N3 and O2 atoms in analogous positions, and simultaneous binding to N3 and N2 in guanines is extremely rare. Contacts with two consecutive nucleotides are much more frequent than base-sugar contacts within one nucleotide. The probable reason for this is the large energy of deformation of hydrogen bonds for the one nucleotide motif. Contacts of Arg, the most frequent amino acid ligand, are stereochemically indistinguishable from the binding of the remaining amino acids except asparagine (Asn) and phenylalanine (Phe). Asn and Phe bind in distinct ways, mostly to a deformed DNA, as in the complexes of TATA-box binding proteins. DNA deformation concentrates on dinucleotide regions with a distinct deformation of the delta and epsilon backbone torsion angles for the Asn and delta, epsilon, zeta and chi for the Phe-contacted regions.

Amino Acids↗