Researchers at the University of Illinois have designed a small molecule that blocks an aberrant pathway associated with myotonic dystrophy type 1, the most common form of muscular dystrophy.

The new compound, soon to be tested in cells, binds tightly to its target, an abnormally elongated RNA that hijacks part of the normal cellular machinery and brings on symptoms of the disease. The newly developed compound is the first to show high selectivity in binding the target while not disrupting other important RNA functions. The study appears this week in the Proceedings of the National Academy of Sciences.

Myotonic dystrophy type 1, a muscle degeneration disease that so far is untreatable, affects about one in 8,000 people worldwide. Some cases are mild, but others lead to a debilitating loss of muscle control, declines in organ function and other potentially life-threatening conditions.

Scientists have recently identified a primary causative agent of the disease, a mutant version of a gene, called DMPK, which contains an excessive number of tri-nucleotide repeats. Nucleotides are the chemical letters that spell out the sequence of a gene, and the normal version of the DMPK gene includes five to 34 cytosine-thymine-guanine (CTG) repeats. The mutant version of the gene includes 50 to as many as 10,000 CTG repeats.

When the mutant DMPK is transcribed into RNA, the first step toward building a protein, these (now CUG) repeats bind to a cellular protein, MBNL, which normally splices other RNA transcripts. The bound MBNL cannot function properly, causing a cascade of negative effects in the cell. Improperly spliced RNAs lead to improperly formed proteins.

Preventing the MBNL protein from binding to the CUG repeats has been shown to ease the symptoms of the disease. The CUG repeats in the aberrant RNA are an ideal target for drug development because they are not found in any other known RNA molecule, Baranger said.

In the course of basic research into compounds that bind to DNA or RNA, the researchers designed a molecule that would selectively bind to T-T or U-U mismatches in DNA or RNA, respectively. (Mismatches occur when two nucleotides in a double-stranded molecule are improperly paired, as occurs in the CTG repeats in the mutant DNA and the CUG repeats in the RNA.) Their compound, which they call Ligand 1, binds to the region of excessive repeats in both the RNA and DNA from the aberrant DMPK gene. More importantly, Ligand 1 prevents the MBNL protein from binding to the RNA.

Further tests revealed that the new compound has significantly lower affinity for other mismatches in DNA or RNA. Baranger's lab also tested the compound on other normal protein-RNA complexes, and found that it did not disrupt those interactions.

Source: http://chemistry.illinois.edu/news/Zimm_MDT090909.html

Two of the MPQC (Massively Parralel Quantum Chemistry) authors, Ida M. B. Nielsen and Curtis L. Janssen, have published the book "Parallel Computing in Quantum Chemistry". MPQC is the open source code which powers hBar Lab services. The book illustrates the use of parallel computing in quantum chemistry with a special attention to different parallelization schemes.

The Publisher says:

Exploring the challenges of parallel programming from the perspective of quantum chemists, Parallel Computing in Quantum Chemistry thoroughly covers topics relevant to designing and implementing parallel quantum chemistry programs.

Focusing on good parallel program design and performance analysis, the first part of the book deals with parallel computer architectures and parallel computing concepts and terminology. The authors discuss trends in hardware, methods, and algorithms; parallel computer architectures and the overall system view of a parallel computer; message-passing; parallelization via multi-threading; measures for predicting and assessing the performance of parallel algorithms; and fundamental issues of designing and implementing parallel programs.

The second part contains detailed discussions and performance analyses of parallel algorithms for a number of important and widely used quantum chemistry procedures and methods. The book presents schemes for the parallel computation of two-electron integrals, details the Hartree-Fock procedure, considers the parallel computation of second-order Møller-Plesset energies, and examines the difficulties of parallelizing local correlation methods.

Through a solid assessment of parallel computing hardware issues, parallel programming practices, and implementation of key methods, this invaluable book enables readers to develop efficient quantum chemistry software capable of utilizing large-scale parallel computers.

Tamiflu is an antiviral drug belonging to a group of drugs called neuraminidase inhibitors. It targets a protein called neuraminidase that lives on the flu virus cells. The protein helps the flu virus break through the cell walls so it can move on to other cells and replicate itself. Tamiflu inhibits the neuraminidase protein, so that the virus can't leave the cell to infect other cells. Eventually, the virus dies.

Tamiflu can't stop the flu entirely. However, studies have shown that if you take it within 48 hours of showing symptoms, it can shorten the duration of the flu. Patients with the flu who took it felt better 30 percent (or 1.3 days) faster than people who didn't take it. The drug also can help protect you from getting the flu if you're exposed to someone who has it.

The Royal Academy of Science announced that the Nobel Prize for Chemistry 2009 has been given to two US citizens Venkatraman Ramakrishnan, Thomas A Steitz and the Israeli Ada E Yonath for their unique "studies of the structure and function of the ribosome". One of the core processes in life.

The three chemistry laureates used X-ray crystallography to map the position of each of the hundreds of thousands of atoms that make up the ribosomes. Their three-dimensional models, built up during the 1980s and 1990s, showed scientists how the ribosomes “read” the genetic code of DNA and converts it to the protein molecules that control all biochemical processes.

The models have been used to develop new antibiotics, some of which are in clinical trials.