Water-mediated ribonucleotide-amino acid pairs and higher-order structures at the RNA-protein interface: analysis of the crystal structure database and a topological classification.

Water is essential for the formation, stability and function of RNA-protein complexes. To delineate the structural role of water molecules in shaping the interactions between RNA and proteins, we comprehensively analyzed a dataset of 329 crystal structures of these complexes to identify water-mediated hydrogen-bonded contacts at RNA-protein interface. Our survey identified a total of 4963 water bridges.

Decoding the enigma of RNA-protein recognition: quantum chemical insights into arginine fork motifs.

Arginine (Arg) forks are noncovalent recognition motifs wherein an Arg interacts with the phosphates and guanine nucleobases of RNA, providing extraordinary specific RNA:protein recognition. In this work, we carried out an in-depth DFT based quantum mechanical investigation on all known classes of Arg forks to estimate their intrinsic structural stabilities and interaction energies. The optimized structures closely mimic the structural characteristics of Arg forks and this close match between experimental and optimized geometries suggests that Arg forks are intrinsically stable and do not require additional support from other RNA or protein components.

Isolation of quinic acid from dropped Blanco fruits: its derivatization, antibacterial potential, docking studies, and ADMET profiling.

dropped fruits are generally discarded as waste, causing environmental pollution and losses to farmers. In the present study, column chromatography has been used to isolate quinic acid (1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid) from the ethyl acetate fraction of a methanol extract of citrus fruits dropped in April. Quinic acid is a ubiquitous plant metabolite found in various plants and microorganisms.

An Atlas of the base inter-RNA stacks involved in bacterial translation.

Nucleobase-specific noncovalent interactions play a crucial role in translation. Herein, we provide a comprehensive analysis of the stacks between different RNA components in the crystal structures of the bacterial ribosome caught at different translation stages. Analysis of tRNA||rRNA stacks reveals distinct behaviour; both the A-and E-site tRNAs exhibit unique stacking patterns with 23S rRNA bases, while P-site tRNAs stack with 16S rRNA bases.

3D Porous MoS-Decorated Reduced Graphene Oxide Aerogel as a Heterogeneous Catalyst for Reductive Transformation Reactions.

The MoS-based reduced graphene oxide aerogel (MoS-rGOA)-assisted organic transformation reactions are presented. MoS-rGOA is used as a heterogeneous catalyst for the reduction of benzene derivatives such as benzaldehyde, nitrobenzene, and benzonitrile to benzyl alcohol, aniline, and benzamide and their derivatives, respectively, in green solvents (water/methanol) and green reducing agents (hydrazine hydrate having N and H as byproducts). The mechanistic features of the reduction pathway, substrate scope, and the best suitable conditions by varying the temperature, solvent, reducing agent, catalyst loading, time, etc.

Structural Mapping of the Base Stacks Containing Post-transcriptionally Modified Bases in RNA.

Post-transcriptionally modified bases play vital roles in many biochemical processes involving RNA. Analysis of the non-covalent interactions associated with these bases in RNA is crucial for providing a more complete understanding of the RNA structure and function; however, the characterization of these interactions remains understudied. To address this limitation, we present a comprehensive analysis of base stacks involving all crystallographic occurrences of the most biologically relevant modified bases in a large dataset of high-resolution RNA crystal structures.

Occurrence and classification of T-shaped interactions between nucleobases in RNA structures.

Understanding the frequency and structural context of discrete noncovalent interactions between nucleotides is of pivotal significance in establishing the rules that govern RNA structure and dynamics. Although T-shaped contacts (i.e.

Structural and Energetic Features of Base-Base Stacking Contacts in RNA.

Nucleobase π-π stacking is one of the crucial organizing interactions within three-dimensional (3D) RNA architectures. Characterizing the structural variability of these contacts in RNA crystal structures will help delineate their subtleties and their role in determining function. This analysis of different stacking geometries found in RNA X-ray crystal structures is the largest such survey to date; coupled with quantum-mechanical calculations on typical representatives of each possible stacking arrangement, we determined the distribution of stacking interaction energies.

Guanidinium-amino acid hydrogen-bonding interactions in protein crystal structures: implications for guanidinium-induced protein denaturation.

In the present work, 86 available high resolution X-ray structures of proteins that contain one or more guanidinium ions (Gdm) are analyzed for the distribution and nature of noncovalent interactions between Gdm and amino-acid residues. A total of 1044 hydrogen-bonding interactions were identified, of which 1039 are N-H⋯O, and five are N-H⋯N. Acidic amino acids are more likely to interact with Gdm (46% of interactions, 26% Asp and 20% Glu), followed by Pro (19% of interactions).

Novel Vanillin-based hybrids inhibit quorum sensing and silences phenotypical expressions in Pseudomonas aeruginosa.

In this study, we report the chemical synthesis, computational analysis, and anti-virulent studies of five Vanillin-based hybrids employing phytochemicals. Vanillin (V) is known to have substantial anti-quorum sensing activity against the gram-negative pathogen Pseudomonas aeruginosa. Therefore, with the aim to further enhance the potency of Vanillin, it was chemically conjugated via a triazole (T) linker with five phytochemicals- Zingerone (Z), Eugenol (E), Guaiacol (G), Cinnamaldehyde (C), and Ferulic acid (F) to form the hybrids named as VTZ (1), VTE (2), VTG (3), VTC (4), and VTF (5), respectively.

Structural Properties of Hachimoji Nucleic Acids and Their Building Blocks: Comparison of Genetic Systems with Four, Six and Eight Alphabets.

Expansion of the genetic alphabet is an ambitious goal. A recent breakthrough has led to the eight-base (hachimoji) genetics having canonical and unnatural bases. However, very little is known on the molecular-level features that facilitate the candidature of unnatural bases as genetic alphabets.

Exploring the Nature of Hydrogen Bonding between RNA and Proteins: A Comprehensive Analysis of RNA : Protein Complexes.

A nonredundant dataset of ∼300 high (up to 2.5 Å) resolution X-ray structures of RNA : protein complexes were analyzed for hydrogen bonds between amino-acid residues and canonical ribonucleotides (rNs). The identified 17100 contacts were classified based on the identity (rA, rC, rG or rU) and interacting fragment (base, sugar, or ribose) of the rN, the nature (polar or nonpolar) and interacting moiety (main chain or side chain) of the amino-acid residue, as well as the rN and amino-acid atoms participating in the hydrogen bonding.

Molecular Dynamics Simulations of the Aptamer Domain of Guanidinium Ion Binding Riboswitch -III: Structural Insights into the Discrimination of Cognate and Alternate Ligands.

Guanidinium ion is a toxic cellular metabolite. The -III riboswitch, an mRNA stretch, regulates the gene expression by undergoing a conformational change in response to the binding of a free guanidinium ion and thereby plays a potentially important role in alleviating guanidinium toxicity in cells. An experimental crystal structure of the guanidinium-bound aptamer domain of the riboswitch from revealed the overall RNA architecture and mapped the specific noncovalent interactions that stabilize the ligand within the binding pocket aptamer.

Role of Stacking Interactions in the Stability of Primitive Genetics: A Quantum Chemical View.

The origin of genetic material on earth is an age-old, entangled mystery that lacks a unanimous explanation. Recent studies have suggested that noncanonical bases such as barbituric acid (BA), melamine (MM), cyanuric acid (CA), and 2,4,6-triaminopyrimidine (TAP) may have undergone molecular selection within the "prebiotic soup" to spontaneously form supramolecular assemblies, which then covalently assembled into an RNA-like polymer (preRNA). However, information on the role of intrinsic interactions of these candidate heterocycles in their molecular selection as the components of preRNA, and the subsequent transition from preRNA to RNA, is currently missing in the literature.

Influence of the Number, Nature and Position of Methyl Posttranscriptional Modifications on Nucleobase Stacking in RNA.

DFT calculations are employed to quantify the influence of the presence, number, nature, and position of posttranscriptional methylation on stacking strength of RNA bases. We carry out detailed potential energy scans of the variation in stacking energies with characteristic geometrical parameters in three categories of forty stacked dimers - canonical base homodimers (N||N), methylated base homodimers (mN||mN) and heterodimers of canonical bases and methylated counterparts (N||mN). Our analysis reveals that neutral methylation invariably enhances the stacking of bases.

On the Nature of Nucleobase Stacking in RNA: A Comprehensive Survey of Its Structural Variability and a Systematic Classification of Associated Interactions.

The astonishing diversity in folding patterns of RNA three-dimensional (3D) structures is crafted by myriads of noncovalent contacts, of which base pairing and stacking are the most prominent. A systematic and comprehensive classification and annotation of these interactions is necessary for a molecular-level understanding of their roles. However, unlike in the case of base pairing, where a widely accepted nomenclature and classification scheme exists in the public domain, currently available classification schemes for base-base stacking need major enhancements to comprehensively capture the necessary features underlying the rich stacking diversity in RNA.

Can modified DNA base pairs with chalcogen bonding expand the genetic alphabet? A combined quantum chemical and molecular dynamics simulation study.

A comprehensive (DFT and MD) computational study is presented with the goal to design and analyze model chalcogen-bonded modified nucleobase pairs that replace one (i.e., A:T, G:C, G:C) or two (G:C, X/X' = S, Se and Y/Y' = F, Cl, Br) Watson-Crick (WC) hydrogen bonds of the canonical A:T or G:C pair with chalcogen bond(s).

Replication of the Aristolochic Acid I Adenine Adduct (ALI-N-A) by a Model Translesion Synthesis DNA Polymerase: Structural Insights on the Induction of Transversion Mutations from Molecular Dynamics Simulations.

Exposure to aristolochic acid I and II (AAI and AAII) has been implicated in aristolochic acid nephropathy and urothelial carcinoma. The toxicological effects of AAs are attributed to their ability to form aristolacatam (AL)-purine DNA adducts. Among these lesions, the AL-adenine (ALI-N-A and ALII-N-A) adducts cause the "signature" A → T transversion mutations associated with AA genotoxicity.

A quantum chemical view of the interaction of RNA nucleobases and base pairs with the side chains of polar amino acids.

Hydrogen bonding between amino acids and nucleobases is important for RNA-protein recognition. As a first step toward understanding the physicochemical features of these contacts, the present work employs density functional theory calculations to critically analyze the intrinsic structures and strength of all theoretically possible model hydrogen-bonded complexes involving RNA nucleobase edges and polar amino acid side chains. Our geometry optimizations uncover a number of unique complexes that involve variable hydrogen-bonding characteristics, including conventional donor-acceptor interactions, bifurcated interactions and single hydrogen-bonded contacts.

Structural Patterns and Stabilities of Hydrogen-Bonded Pairs Involving Ribonucleotide Bases and Arginine, Glutamic Acid, or Glutamine Residues of Proteins from Quantum Mechanical Calculations.

Ribonucleotide:protein interactions play crucial roles in a number of biological processes. Unlike the RNA:protein interface where van der Waals contacts are prevalent, the recognition of a single ribonucleotide such as ATP by a protein occurs predominantly through hydrogen-bonding interactions. As a first step toward understanding the role of hydrogen bonding in ribonucleotide:protein recognition, the present work employs density functional theory to provide a detailed quantum-mechanical analysis of the structural and energetic characteristics of 18 unique hydrogen-bonded pairs involving the nucleobase/nucleoside moiety of four canonical ribonucleotides and the side chains of three polar amino-acid residues (arginine, glutamine, and glutamic acid) of proteins.

Radical pathways for the formation of non-canonical nucleobases in prebiotic environments.

Due to the inability of canonical nucleobases (adenine, uracil, guanine and cytosine) to spontaneously form ribonucleosides and base pairs in free form in solution, RNA is believed to be preceded by a primitive information polymer (preRNA). The preRNA is proposed to contain non-canonical, heterocyclic bases that possess the above-mentioned capabilities. An extensive search for such candidate heterocycles has recently revealed that barbituric acid (BA), melamine (MM) and 2,4,6-triaminopyrimidine (TAP) have the capability to spontaneously form ribonucleosides and supramolecular assemblies that are held by Watson-Crick type hydrogen-bonded base pairs involving BA, MM, TAP and cyanuric acid (CA) heterocycles.

Could Purines Be Formed from Cyanamide and Cyanoacetylene in a Prebiotic Earth Environment?

Knowledge of prebiotic nucleobase formation is important for understanding the origin of contemporary genetics. Observation of nucleobase precursor radicals in previous impact laser plasma simulations of the late heavy bombardment period (FerusProc. Natl.

Pairing interactions between nucleobases and ligands in aptamer:ligand complexes of riboswitches: crystal structure analysis, classification, optimal structures, and accurate interaction energies.

In the present work, 67 crystal structures of the aptamer domains of RNA riboswitches are chosen for analysis of the structure and strength of hydrogen bonding (pairing) interactions between nucleobases constituting the aptamer binding pockets and the bound ligands. A total of 80 unique base:ligand hydrogen-bonded pairs containing at least two hydrogen bonds were identified through visual inspection. Classification of these contacts in terms of the interacting edge of the aptamer nucleobase revealed that interactions involving the Watson-Crick edge are the most common, followed by the sugar edge of purines and the Hoogsteen edge of uracil.

Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.

Ochratoxin A (OTA) is a ubiquitous food toxin associated with chronic nephropathy in humans and renal carcinogenicity in rodents. The mutational spectra of cells exposed to OTA reveal that one-base deletions comprise the largest percentage (73%) of the total mutations that occur upon OTA exposure. To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (ition prod) at the C-site of guanine.

Can Cyanuric Acid and 2,4,6-Triaminopyrimidine Containing Ribonucleosides be Components of Prebiotic RNA? Insights from QM Calculations and MD Simulations.

As a step toward assessing their fitness as pre-RNA nucleobases, we employ DFT and MD simulations to analyze the noncovalent interactions of cyanuric acid (CA) and 2,4,6-triaminopyrimidine (TAP), and the structural properties of the associated ribonucleosides (rNs) and oligonucleotides. Our calculations reveal that the TAP : CA pair has a comparable hydrogen-bond strength to the canonical A : U pair. This strengthens the candidature of CA and TAP as prebiotic nucleobases.