New restraints and validation approaches for nucleic acid structures in PDB-REDO

The quality of macromolecular structure models crucially depends on refinement and validation targets, which optimally describe the expected chemistry. Commonly used software for these two procedures has been designed and developed in a protein-centric manner, resulting in relatively few established features for the refinement and validation of nucleic acid-containing structure models. Here, new nucleic acid-specific approaches implemented in PDB-REDO are described, including a new restraint model using noncovalent geometries (base-pair hydrogen bonding and base-pair stacking) as refinement targets. New validation routines are also presented, including a metric for Watson–Crick base-pair geometry normality (Z bpG). Applying the PDB-REDO pipeline with the new restraint model to the whole Protein Data Bank (PDB) demonstrates an overall positive effect on the quality of nucleic acid-containing structure models. Finally, we discuss examples of improvements in the geometry of specific nucleic acid structures in the PDB. The new PDB-REDO models and pipeline are available at https://pdb-redo.eu/.

DNA structural and physical properties reveal peculiarities in promoter sequences of the bacterium Escherichia coli K-12

The gene transcription of bacteria starts with a promoter sequence being recognized by a transcription factor found in the RNAP enzyme, this process is assisted through the conservation of nucleotides as well as other factors governing these intergenic regions. Faced with this, the coding of genetic information into physical aspects of the DNA such as enthalpy, stability, and base-pair stacking could suggest promoter activity as well as protrude differentiation of promoter and non-promoter data. In this work, a total of 3131 promoter sequences associated to six different sigma factors in the bacterium E. coli were converted into numeric attributes, a strong set of control sequences referring to a shuffled version of the original sequences as well as coding regions is provided. Then, the parameterized genetic information was normalized, exhaustively analyzed through statistical tests. The results suggest that strong signals in the promoter sequences match the binding site of transcription factor proteins, indicating that promoter activity is well represented by its conversion into physical attributes. Moreover, the features tested in this report conveyed significant variances between promoter and control data, enabling these features to be employed in bacterial promoter classification. The results produced here may aid in bacterial promoter recognition by providing a robust set of biological inferences.

AFM Images of Viroid-Sized Rings That Self-Assemble from Mononucleotides through Wet–Dry Cycling: Implications for the Origin of Life

It is possible that early life relied on RNA polymers that served as ribozyme-like catalysts and for storing genetic information. The source of such polymers is uncertain, but previous investigations reported that wet–dry cycles simulating prebiotic hot springs provide sufficient energy to drive condensation reactions of mononucleotides to form oligomers. The aim of the study reported here was to visualize the products by atomic force microscopy. In addition to globular oligomers, ring-like structures ranging from 10–200 nm in diameter, with an average around 30–40 nm, were abundant, particularly when nucleotides capable of base pairing were present. The thickness of the rings was consistent with single stranded products, but some had thicknesses indicating base pair stacking. Others had more complex structures in the form of short polymer attachments and pairing of rings. These observations suggest the possibility that base-pairing may promote polymerization during wet–dry cycling followed by solvation of the rings. We conclude that RNA-like rings and structures could have been synthesized non-enzymatically on the prebiotic Earth, with sizes sufficient to fold into ribozymes and genetic molecules required for life to begin.

Interfacing DNA with Gold Nanoparticles for Heavy Metal Detection

The contamination of heavy metals (e.g., Hg, Pb, Cd and As) poses great risks to the environment and human health. Rapid and simple detection of heavy metals of considerable toxicity in low concentration levels is an important task in biological and environmental analysis. Among the many convenient detection methods for heavy metals, DNA-inspired gold nanoparticles (DNA-AuNPs) have become a well-established approach, in which assembly/disassembly of AuNPs is used for colorimetric signaling of the recognition event between DNA and target heavy metals at the AuNP interface. This review focuses on the recent efforts of employing DNA to manipulate the interfacial properties of AuNPs, as well as the major advances in the colorimetric detection of heavy metals. Beginning with the introduction of the fundamental aspects of DNA and AuNPs, three main strategies of constructing DNA-AuNPs with DNA binding-responsive interface are discussed, namely, crosslinking, electrostatic interaction and base pair stacking. Then, recent achievements in colorimetric biosensing of heavy metals based on manipulation of the interface of DNA-AuNPs are surveyed and compared. Finally, perspectives on challenges and opportunities for future research in this field are provided.

Viroid-sized rings self-assemble from mononucleotides through wet-dry cycling: implications for the origin of life

It is possible that early life relied on RNA polymers that served as ribozyme-like catalysts and store genetic information1,2. The source of such polymers is uncertain, but previous investigations reported that wet-dry cycles simulating prebiotic hot springs provide sufficient energy to drive condensation reactions of mononucleotides to form oligomers3. The aim of the study reported here was to visualize the products by atomic force microscopy. In addition to globular oligomers, ring-like structures ranging from 10-200 nm in diameter with an average around 30-40 nm were abundant, particularly when nucleotides capable of base pairing were present. The thickness of the rings was consistent with single stranded products, but some had thicknesses indicating base pair stacking. Others had more complex structures in the form of short polymer attachments and pairing of rings. These observations suggest the possibility that template-directed synthesis may occur during wet-dry cycling followed by solvation of the rings. We conclude that RNA-like rings and structures could have been synthesized non-enzymatically on the prebiotic Earth with sizes sufficient to fold into ribozymes and genetic molecules required for life to begin.

Electronic Structure Change in DNA Caused by Base Pair Motions and Its Effect on Charge Transfer in DNA Chains

One important aspect of carrier transfer in DNA is its coupling with atomic motions. The collective motion of the base pairs can either improve the charge transfer by enhancing the π stacking between the bases, or trap the carriers due to strong coupling. By utilizing a pseudo-helical base pair stack model, we systematically studied the electronic structure and its dependence to geometry changes that represent the important DNA motions, including the translation, the twist and the torsion of the base pairs. Our calculations reveal that the above motions may significantly change the electron structure and affect their transport properties. In order to improve the transport of carriers in DNA so that it can become a prospective material in future electronics, it is necessary to make large changes to the atomic structure. Our calculations of the electronic structure under large geometry variation, including large base pair stacking deformation and the insertion of phenyl rings in the bases, can provide good guidelines for such structural modifications of DNA.