Discovering functional motifs in long noncoding RNAs.

Long noncoding RNAs (lncRNAs) are products of pervasive transcription that closely resemble messenger RNAs on the molecular level, yet function through largely unknown modes of action. The current model is that the function of lncRNAs often relies on specific, typically short, conserved elements, connected by linkers in which specific sequences and/or structures are less important. This notion has fueled the development of both computational and experimental methods focused on the discovery of functional elements within lncRNA genes, based on diverse signals such as evolutionary conservation, predicted structural elements, or the ability to rescue loss-of-function phenotypes.

GTP Cyclohydrolase I as a Potential Drug Target: New Insights into Its Allosteric Modulation via Normal Mode Analysis.

Guanosine triphosphate (GTP) cyclohydrolase I (GCH1) catalyzes the conversion of GTP into dihydroneopterin triphosphate (DHNP). DHNP is the first intermediate of the folate de novo biosynthesis pathway in prokaryotic and lower eukaryotic microorganisms and the tetrahydrobiopterin (BH4) biosynthesis pathway in higher eukaryotes. The de novo folate biosynthesis provides essential cofactors for DNA replication, cell division, and synthesis of key amino acids in rapidly replicating pathogen cells, such as , a causative agent of malaria.

Uncovering deeply conserved motif combinations in rapidly evolving noncoding sequences.

Background: Animal genomes contain thousands of long noncoding RNA (lncRNA) genes, a growing subset of which are thought to be functionally important. This functionality is often mediated by short sequence elements scattered throughout the RNA sequence that correspond to binding sites for small RNAs and RNA binding proteins. Throughout vertebrate evolution, the sequences of lncRNA genes changed extensively, so that it is often impossible to obtain significant alignments between sequences of lncRNAs from evolutionary distant species, even when synteny is evident.

Probing the Structural Dynamics of the Tunneling-Fold Enzyme 6-Pyruvoyl Tetrahydropterin Synthase to Reveal Allosteric Drug Targeting Sites.

The folate synthesis pathway is a well-established drug target in the treatment of many infectious diseases. Antimalarial antifolate drugs have proven to be effective against malaria, however, rapid drug resistance has emerged on the two primary targeted enzymes: dihydrofolate reductase and dihydroptoreate synthase. The need to identify alternative antifolate drugs and novel metabolic targets is of imminent importance.

Unraveling the Motions behind Enterovirus 71 Uncoating.

Enterovirus 71 can be a severe pathogen in small children and immunocompromised adults. Virus uncoating is a critical step in the infection of the host cell; however, the mechanisms that control this process remain poorly understood. We applied normal mode analysis and perturbation response scanning to several complexes of the virus capsid and present a coarse-graining approach to analyze the full capsid.

The importance of XRCC2 in RAD51-related DNA damage repair.

The repair of DNA damage by homologous recombination (HR) is a key pathway for the maintenance of genetic stability in mammalian cells, especially during and following DNA replication. The central HR protein is RAD51, which ensures high fidelity DNA repair by facilitating strand exchange between damaged and undamaged homologous DNA segments. Several RAD51-like proteins, including XRCC2, appear to help with this process, but their roles are not well understood.