Water plays an important role in stabilizing the structure of DNA and mediating its interactions. Here, the hydration of DNA was analyzed in terms of dinucleotide fragments from an ensemble of 2727 nonredundant DNA chains containing 41 853 dinucleotides and 316 265 associated first-shell water molecules. The dinucleotides were classified into categories based on their 16 sequences and the previously determined structural classes known as nucleotide conformers (NtCs). The construction of hydrated dinucleotide building blocks allowed dinucleotide hydration to be calculated as the probability of water density distributions. Peaks in the water densities, known as hydration sites (HSs), uncovered the interplay between base and sugar-phosphate hydration in the context of sequence and structure. To demonstrate the predictive power of hydrated DNA building blocks, they were then used to predict hydration in an independent set of crystal and NMR structures. In ten tested crystal structures, the positions of predicted HSs and experimental waters were in good agreement (more than 40% were within 0.5 Å) and correctly reproduced the known features of DNA hydration, for example the `spine of hydration' in B-DNA. Therefore, it is proposed that hydrated building blocks can be used to predict DNA hydration in structures solved by NMR and cryo-EM, thus providing a guide to the interpretation of experimental data and computer models. The data for the hydrated building blocks and the predictions are available for browsing and visualization at the website https://watlas.datmos.org/watna/.

• Klíčová slova
• DNA hydration, WatNA, dinucleotide fragments, knowledge-based prediction, water,
• MeSH
• DNA * chemie   MeSH
• konformace nukleové kyseliny MeSH
• nukleotidy MeSH
• voda * chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA * MeSH
• nukleotidy MeSH
• voda * MeSH

In this review, we describe the creation of the Nucleic Acid Database (NDB) at Rutgers University and how it became a testbed for the current infrastructure of the RCSB Protein Data Bank. We describe some of the special features of the NDB and how it has been used to enable research. Plans for the next phase as the Nucleic Acid Knowledgebase (NAKB) are summarized.

• Klíčová slova
• DNA, RNA, biological structure database, nucleic acid conformation, nucleic acid structures, validation standards,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

With both catalytic and genetic functions, ribonucleic acid (RNA) is perhaps the most pluripotent chemical species in molecular biology, and its functions are intimately linked to its structure and dynamics. Computer simulations, and in particular atomistic molecular dynamics (MD), allow structural dynamics of biomolecular systems to be investigated with unprecedented temporal and spatial resolution. We here provide a comprehensive overview of the fast-developing field of MD simulations of RNA molecules. We begin with an in-depth, evaluatory coverage of the most fundamental methodological challenges that set the basis for the future development of the field, in particular, the current developments and inherent physical limitations of the atomistic force fields and the recent advances in a broad spectrum of enhanced sampling methods. We also survey the closely related field of coarse-grained modeling of RNA systems. After dealing with the methodological aspects, we provide an exhaustive overview of the available RNA simulation literature, ranging from studies of the smallest RNA oligonucleotides to investigations of the entire ribosome. Our review encompasses tetranucleotides, tetraloops, a number of small RNA motifs, A-helix RNA, kissing-loop complexes, the TAR RNA element, the decoding center and other important regions of the ribosome, as well as assorted others systems. Extended sections are devoted to RNA-ion interactions, ribozymes, riboswitches, and protein/RNA complexes. Our overview is written for as broad of an audience as possible, aiming to provide a much-needed interdisciplinary bridge between computation and experiment, together with a perspective on the future of the field.

• MeSH
• DNA chemie   MeSH
• katalýza MeSH
• konformace nukleové kyseliny * MeSH
• počítačová simulace MeSH
• RNA chemie   MeSH
• simulace molekulární dynamiky * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• DNA MeSH
• RNA MeSH

Crystallography provides unique information about the arrangement of water molecules near protein surfaces. Using a nonredundant set of 2818 protein crystal structures with a resolution of better than 1.8 Å, the extent and structure of the hydration shell of all 20 standard amino-acid residues were analyzed as function of the residue conformation, secondary structure and solvent accessibility. The results show how hydration depends on the amino-acid conformation and the environment in which it occurs. After conformational clustering of individual residues, the density distribution of water molecules was compiled and the preferred hydration sites were determined as maxima in the pseudo-electron-density representation of water distributions. Many hydration sites interact with both main-chain and side-chain amino-acid atoms, and several occurrences of hydration sites with less canonical contacts, such as carbon-donor hydrogen bonds, OH-π interactions and off-plane interactions with aromatic heteroatoms, are also reported. Information about the location and relative importance of the empirically determined preferred hydration sites in proteins has applications in improving the current methods of hydration-site prediction in molecular replacement, ab initio protein structure prediction and the set-up of molecular-dynamics simulations.

• Klíčová slova
• X-ray crystallography, protein hydration, structural biology,
• MeSH
• aminokyseliny analýza   MeSH
• databáze proteinů MeSH
• krystalografie rentgenová MeSH
• lidé MeSH
• molekulární konformace MeSH
• molekulární modely MeSH
• proteiny chemie   MeSH
• sekundární struktura proteinů MeSH
• voda analýza   MeSH
• vodíková vazba MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokyseliny MeSH
• proteiny MeSH
• voda MeSH

To investigate the principles driving recognition between proteins and DNA, we analyzed more than thousand crystal structures of protein/DNA complexes. We classified protein and DNA conformations by structural alphabets, protein blocks [de Brevern, Etchebest and Hazout (2000) (Bayesian probabilistic approach for predicting backbone structures in terms of protein blocks. Prots. Struct. Funct. Genet., 41:271-287)] and dinucleotide conformers [Svozil, Kalina, Omelka and Schneider (2008) (DNA conformations and their sequence preferences. Nucleic Acids Res., 36:3690-3706)], respectively. Assembling the mutually interacting protein blocks and dinucleotide conformers into 'interaction matrices' revealed their correlations and conformer preferences at the interface relative to their occurrence outside the interface. The analyzed data demonstrated important differences between complexes of various types of proteins such as transcription factors and nucleases, distinct interaction patterns for the DNA minor groove relative to the major groove and phosphate and importance of water-mediated contacts. Water molecules mediate proportionally the largest number of contacts in the minor groove and form the largest proportion of contacts in complexes of transcription factors. The generally known induction of A-DNA forms by complexation was more accurately attributed to A-like and intermediate A/B conformers rare in naked DNA molecules.

• MeSH
• DNA vazebné proteiny chemie   MeSH
• DNA chemie   MeSH
• fosfáty MeSH
• interpretace statistických dat MeSH
• konformace nukleové kyseliny MeSH
• konformace proteinů MeSH
• molekulární modely MeSH
• vazba proteinů MeSH
• voda chemie   MeSH
• výpočetní biologie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA vazebné proteiny MeSH
• DNA MeSH
• fosfáty MeSH
• voda MeSH

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.

• MeSH
• hořčík chemie   MeSH
• kationty dvojmocné chemie   MeSH
• kationty jednomocné chemie   MeSH
• konformace nukleové kyseliny MeSH
• molekulární modely MeSH
• molekulární sekvence - údaje MeSH
• RNA katalytická chemie   MeSH
• sekvence nukleotidů MeSH
• sodík chemie   MeSH
• vazebná místa MeSH
• virus hepatitidy delta enzymologie   MeSH
• voda chemie   MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• hořčík MeSH
• kationty dvojmocné MeSH
• kationty jednomocné MeSH
• RNA katalytická MeSH
• sodík MeSH
• voda MeSH

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.

• MeSH
• aminokyseliny chemie   metabolismus   MeSH
• chemické modely MeSH
• deoxyribonukleotidy chemie   metabolismus   MeSH
• DNA vazebné proteiny chemie   metabolismus   MeSH
• DNA chemie   metabolismus   MeSH
• dusík chemie   MeSH
• konformace nukleové kyseliny MeSH
• krystalografie rentgenová MeSH
• kyslík chemie   MeSH
• ligandy MeSH
• makromolekulární látky MeSH
• racionální návrh léčiv MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• voda chemie   MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokyseliny MeSH
• deoxyribonukleotidy MeSH
• DNA vazebné proteiny MeSH
• DNA MeSH
• dusík MeSH
• kyslík MeSH
• ligandy MeSH
• makromolekulární látky MeSH
• voda MeSH

Water distributions around phosphate groups in 59 B-, A-, and Z-DNA crystal structures were analyzed. It is shown that the waters are concentrated in six hydration sites per phosphate and that the positions and occupancies of these sites are dependent on the conformation and type of nucleotide. The patterns of hydration that are characteristic of the backbone of the three DNA helical types can be attributed in part to the interactions of these hydration sites.

• MeSH
• DNA chemie   MeSH
• fosfáty chemie   MeSH
• konformace nukleové kyseliny MeSH
• molekulární modely MeSH
• oligodeoxyribonukleotidy chemie   MeSH
• vazebná místa genetika   MeSH
• voda chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Názvy látek
• DNA MeSH
• fosfáty MeSH
• oligodeoxyribonukleotidy MeSH
• voda MeSH