MetBP: a software tool for detection of interaction between metal ion-RNA base pairs.

MOTIVATION: The role of metals in shaping and functioning of RNA is a well-established fact, and the understanding of that through the analysis of structural data has biological relevance. Often metal ions bind to one or more atoms of the nucleobase of an RNA. This fact becomes more interesting when such bases form a base pair with any other base. Furthermore, when metal ions bind to any residue of an RNA, the secondary structural features of the residue (helix, loop, unpaired, etc.) are also biologically important. The available metal-binding-related software tools cannot address such type-specific queries. RESULTS: To fill this limitation, we have designed a software tool, called MetBP that meets the goal. This tool is a stand-alone command-line-based tool and has no dependency on the other existing software. It accepts a structure file in mmCIF or PDB format and computes the base pairs and thereafter reports all metals that bind to one or more nucleotides that form pairs with another. It reports binding distance, angles along with base pair stability. It also reports several other important aspects, e.g. secondary structure of the residue in the RNA. MetBP can be used as a generalized metal-binding site detection tool for Proteins and DNA as well. AVAILABILITY AND IMPLEMENTATION: https://github.com/computational-biology/metbp. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

RNABPDB: Molecular Modeling of RNA Structure-From Base Pair Analysis in Crystals to Structure Prediction.

The stable three-dimensional structure of RNA is known to play several important biochemical roles, from post-transcriptional gene regulation to enzymatic action. These structures contain double-helical regions, which often have different types of non-canonical base pairs in addition to Watson-Crick base pairs. Hence, it is important to study their structures from experimentally obtained or even predicted ones, to understand their role, or to develop a drug against the potential targets. Molecular Modeling of RNA double helices containing non-canonical base pairs is a difficult process, particularly due to the unavailability of structural features of non-Watson-Crick base pairs. Here we show a composite web-server with an associated database that allows one to generate the structure of RNA double helix containing non-canonical base pairs using consensus parameters obtained from the database. The database classification is followed by an evaluation of the central tendency of the structural parameters as well as a quantitative estimation of interaction strengths. These parameters are used to construct three-dimensional structures of double helices composed of Watson-Crick and/or non-canonical base pairs. Our benchmark study to regenerate double-helical fragments of many experimentally derived RNA structures indicate very high accuracy. This composite server is expected to be highly useful in understanding functions of various pre-miRNA by modeling structures of the molecules and estimating binding efficiency. The database can be accessed from http://hdrnas.saha.ac.in/rnabpdb .

Contact networks in RNA: a structural bioinformatics study with a new tool.

Base pairing in RNA are significantly rich and versatile due to the potential non-canonical base pairing amongst nucleotides. Not only that, one base in RNA can pair with more than one bases simultaneously. This opens up a new dimension of research to detect such types of base-base pair networks in RNA and to analyze them. Even if a base do not form a pair, it may have significant extent of [Formula: see text]-[Formula: see text] stacking overlap that can stabilize the structures. In this work, we report a software tool, called BPNet, that accepts a mmCIF or PDB file and computes the base-pair/[Formula: see text]-[Formula: see text] contact network components using graph formalism. The software can run on Linux platform in both serial and parallel modes. It generates several information in suitable file formats for visualization of the networks. This paper describes the BPNet software and also presents some interesting results obtained by analyzing several RNA structures by the software to show its effectiveness.

Stacking geometry between two sheared Watson-Crick basepairs: Computational chemistry and bioinformatics based prediction.

BACKGROUND: Molecular modeling of RNA double helices is possible using most probable values of basepair parameters obtained from crystal structure database. The A:A w:wC non-canonical basepair, involving Watson-Crick edges of two Adenines in cis orientation, appears quite frequently in database. Bimodal distribution of its Shear, due to two different H-bonding schemes, introduces the confusion in assigning most the probable value. Its effect is pronounced when the A:A w:wC basepair stacks on Sheared wobble G:U W:WC basepairs. METHODS: We employed molecular dynamics simulations of three possible double helices with GAG, UAG and GAU sequence motifs at their centers and quantum chemical calculation for non-canonical A:A w:wC basepair stacked on G:U W:WC basepair. RESULTS: We noticed stable structures of GAG motif with specifically negative Shear of the A:A basepair but stabilities of the other motifs were not found with A:A w:wC basepairing. Hybrid DFT-D and MP2 stacking energy analyses on dinucleotide step sequences, A:A w:wC::G:U W:WC and A:A w:wC::U:G W:WC reveal that viable orientation of A:A::G:U prefers one of the H-bonding modes with negative Shear, supported by crystal structure database. The A:A::U:G dinucleotide, however, prefers structure with only positive Shear. CONCLUSIONS: The quantum chemical calculations explain why MD simulations of GAG sequence motif only appear stable. In the cases of the GAU and UAG motifs "tug of war" situation between positive and negative Shears of A:A w:wC basepair induces conformational plasticity. GENERAL SIGNIFICANCE: We have projected comprehensive reason behind the promiscuous nature of A:A w:wC basepair which brings occasional structural plasticity.