Computational Design of Allosteric Ribozymes via Genetic Algorithms.

In vitro selection of allosteric ribozymes has many challenges, such as complex and time-consuming experimental procedures, uncertain results, and the unwanted functionality of the enriched sequences. The precise computational design of allosteric ribozymes is achievable using RNA secondary structure folding principles. The computational design of allosteric ribozymes is based on experimentally validated EAs, random search algorithms, and a partition function for RNA folding.

Antisense and Functional Nucleic Acids in Rational Drug Development.

This review is focused on antisense and functional nucleic acid used for completely rational drug design and drug target assessment, aiming to reduce the time and money spent and increase the successful rate of drug development. Nucleic acids have unique properties that play two essential roles in drug development as drug targets and as drugs. Drug targets can be messenger, ribosomal, non-coding RNAs, ribozymes, riboswitches, and other RNAs.

Targeting FMN, TPP, SAM-I, and glmS Riboswitches with Chimeric Antisense Oligonucleotides for Completely Rational Antibacterial Drug Development.

Antimicrobial drug resistance has emerged as a significant challenge in contemporary medicine due to the proliferation of numerous bacterial strains resistant to all existing antibiotics. Meanwhile, riboswitches have emerged as promising targets for discovering antibacterial drugs. Riboswitches are regulatory elements in certain bacterial mRNAs that can bind to specific molecules and control gene expression via transcriptional termination, prevention of translation, or mRNA destabilization.

GHOST-NOT and GHOST-YES: Two programs for generating high-speed biosensors with randomized oligonucleotide binding sites with NOT or YES Boolean logic functions based on experimentally validated algorithms.

High-speed allosteric hammerhead ribozymes can be engineered to distinguish well between a perfectly matching effector and the nucleic acid sequences with a few mismatches under physiologically relevant conditions. Such ribozymes can be designed to control the expression of exogenous mRNAs and can be used to develop new gene therapies, including anticancer treatments. The in vivo selection of such ribozymes is a complicated and lengthy procedure with no guarantee of success.

Bioinformatics and Genomic Analyses of the Suitability of Eight Riboswitches for Antibacterial Drug Targets.

Antibiotic resistance (AR) is an acute problem that results in prolonged and debilitating illnesses. AR mortality worldwide is growing and causes a pressing need to research novel mechanisms of action and untested target molecules. This article presents in silico analyses of eight bacterial riboswitches for their suitability for antibacterial drug targets.

Versatile tools of synthetic biology applied to drug discovery and production.

Although synthetic biology is an emerging research field, which has come to prominence within the last decade, it already has many practical applications. Its applications cover the areas of pharmaceutical biotechnology and drug discovery, bringing essential novel methods and strategies such as metabolic engineering, reprogramming the cell fate, drug production in genetically modified organisms, molecular glues, functional nucleic acids and genome editing. This review discusses the main avenues for synthetic biology application in pharmaceutical biotechnology.

RSwitch: A Novel Bioinformatics Database on Riboswitches as Antibacterial Drug Targets.

The RSwitch is a MySQL database implemented on a PHP-based server, which also provides various useful tools for analyses of DNA, RNA, and protein sequences applying a user-friendly interface. The RSwitch database currently contains information and annotations of 215 bacterial riboswitches from 16 different types found in 50 human pathogenic bacteria. The riboswitch classes include those sensing FMN, glmS, Cobalamin, Lysine, SAH, SAM, Purine, TPP, c-di-GMPI, c-di-GMPII, Moco, PreQ1, Fluoride, Glycine, Mg, and Mn type of bacterial riboswitches.

Riboswitch distribution, structure, and function in bacteria.

Riboswitches are gene control elements that directly bind to specific ligands to regulate gene expression without the need for proteins. They are found in all three domains of life, including Bacteria, Archaea, and Eukaryota. Riboswitches are mostly spread in bacteria and archaea.

Genome-wide bioinformatics analysis of FMN, SAM-I, glmS, TPP, lysine, purine, cobalamin, and SAH riboswitches for their applications as allosteric antibacterial drug targets in human pathogenic bacteria.

: A constantly growing number of antibiotic-resistant strains of human pathogenic bacteria is an acute problem. Prolonged illnesses and increasing mortality worldwide mean that there is an urgent need to develop novel antibacterial drugs based on new targets and mechanisms of action. We present analyses of bacterial riboswitches that may be suitable as antibacterial drug targets.

EBWS: Essential Bioinformatics Web Services for Sequence Analyses.

The Essential Bioinformatics Web Services (EBWS) are implemented on a new PHP-based server that provides useful tools for analyses of DNA, RNA, and protein sequences applying a user-friendly interface. Nine Web-based applets are currently available on the Web server. They include reverse complementary DNA and random DNA/RNA/peptide oligomer generators, a pattern sequence searcher, a DNA restriction cutter, a prokaryotic ORF finder, a random DNA/RNA mutation generator.