Destabilization of the MutSα's protein-protein interface due to binding to the DNA adduct induced by anticancer agent carboplatin via molecular dynamics simulations.

DNA mismatch repair (MMR) proteins maintain genetic integrity in all organisms by recognizing and repairing DNA errors. Such alteration of hereditary information can lead to various diseases, including cancer. Besides their role in DNA repair, MMR proteins detect and initiate cellular responses to certain type of DNA damage.

Non-specificity and synergy at the binding site of the carboplatin-induced DNA adduct via molecular dynamics simulations of the MutSα-DNA recognition complex.

MutSα is the most abundant mismatch-binding factor of human DNA mismatch repair (MMR) proteins. MMR maintains genetic stability by recognizing and repairing DNA defects. Failure to accomplish their function may lead to cancer.

Computational and synthetic studies towards improving rescinnamine as an inducer of MSH2-dependent apoptosis in cancer treatment.

We, and others, have previously shown that mismatch repair proteins, in addition to their repair function, contribute to cell death initiation. In response to some drugs, this cell death activity is independent of the repair function of the proteins. Rescinnamine, a derivative of the indole alkaloid reserpine, a drug used to treat hypertension several decades ago, was shown to target the cell death-initiating activity of mismatch repair proteins.

The molecular origin of the MMR-dependent apoptosis pathway from dynamics analysis of MutSα-DNA complexes.

The cellular response to DNA damage signaling by mismatch-repair (MMR) proteins is incompletely understood. It is generally accepted that MMR-dependent apoptosis pathway in response to DNA damage detection is independent of MMR's DNA repair function. In this study, we investigate correlated motions in response to the binding of mismatched and platinum cross-linked DNA fragments by MutSα, as derived from 50 ns molecular dynamics simulations.

Insights into protein - DNA interactions, stability and allosteric communications: a computational study of mutSα-DNA recognition complexes.

DNA mismatch repair proteins (MMR) maintain genetic stability by recognizing and repairing mismatched bases and insertion/deletion loops mistakenly incorporated during DNA replication, and initiate cellular response to certain types of DNA damage. Loss of MMR in mammalian cells has been linked to resistance to certain DNA damaging chemotherapeutic agents, as well as to increase risk of cancer. Mismatch repair pathway is considered to involve the concerted action of at least 20 proteins.

Microscopic factors that control beta-sheet registry in amyloid fibrils formed by fragment 11-25 of amyloid beta peptide: insights from computer simulations.

Short fragments of amyloidogenic proteins are widely used as model systems in studies of amyloid formation. Fragment 11-25 of the amyloid beta protein involved in Alzheimer's disease (Abeta11-25) was recently shown to form amyloid fibrils composed of anti-parallel beta-sheets. Interestingly, fibrils grown under neutral and acidic conditions were seen to possess different registries of their inter-beta-strand hydrogen bonds.

Structural characterization of Al10O6iBu16(mu-H)2, a high aluminum content cluster: further studies of methylaluminoxane (MAO) and related aluminum complexes.

The first structurally characterized isobutyl-containing aluminoxane compound is presented. The Al10O6iBu16(mu-H)2 (I) cluster is produced from neat octakis-isobutyltetraluminoxane (Al4O2iBu8) at 80 degrees C in 6-8 h followed by slow crystallization. The crystal is triclinic (space group P1) with the molecule lying on an inversion center.

Methyaluminoxane (MAO) polymerization mechanism and kinetic model from ab initio molecular dynamics and electronic structure calculations.

MAO is the co-catalyst in metallocene catalytic systems, which are widely used in single-site olefin polymerization due to their high stereoselectivity. To date, the structures of the catalytically active compound or compounds in MAO have eluded researchers. Although many structural models have been proposed, none are generally accepted.