Role of Inosine⁻Uracil Base Pairs in the Canonical RNA Duplexes.

Adenosine to inosine (A⁻I) editing is the most common modification of double-stranded RNA (dsRNA). This change is mediated by adenosine deaminases acting on RNA (ADARs) enzymes with a preference of U>A>C>G for 5′ neighbor and G>C=A>U or G>C>U=A for 3′ neighbor. A⁻I editing occurs most frequently in the non-coding regions containing repetitive elements such as ALUs.

Protein environment affects the water-tryptophan binding mode. MD, QM/MM, and NMR studies of engrailed homeodomain mutants.

Water molecules can interact with aromatic moieties using either their O-H bonds or their lone-pairs of electrons. In proteins, water-π interactions have been reported to occur with tryptophan and histidine residues, and dynamic exchange between O-Hπ hydrogen bonding and lone-pairπ interactions was suggested to take place, based on ab initio calculations. Here we used classical and QM/MM molecular dynamics simulations, complemented with an NMR study, to examine a specific water-indole interaction observed in the engrailed homeodomain and in its mutants.

DNA mutation motifs in the genes associated with inherited diseases.

Mutations in human genes can be responsible for inherited genetic disorders and cancer. Mutations can arise due to environmental factors or spontaneously. It has been shown that certain DNA sequences are more prone to mutate.

Mechanical Model of DNA Allostery.

The importance of allosteric effects in DNA is becoming increasingly appreciated, but the underlying mechanisms remain poorly understood. In this work, we propose a general modeling framework to study DNA allostery. We describe DNA in a coarse-grained manner by intra-base pair and base pair step coordinates, complemented by groove widths.

μABC: a systematic microsecond molecular dynamics study of tetranucleotide sequence effects in B-DNA.

We present the results of microsecond molecular dynamics simulations carried out by the ABC group of laboratories on a set of B-DNA oligomers containing the 136 distinct tetranucleotide base sequences. We demonstrate that the resulting trajectories have extensively sampled the conformational space accessible to B-DNA at room temperature. We confirm that base sequence effects depend strongly not only on the specific base pair step, but also on the specific base pairs that flank each step.