Homology and molecular dynamics models of toll-like receptor 7 protein and its dimerization.

Toll-like receptor protein 7 is a transmembrane protein playing a crucial role in the signaling pathways involved in innate immunity. Its crystal structure is not yet available, but there are several proteins possessing domains of sufficiently high homology, which enabled us to build a model of the toll-like receptor protein 7 monomer and gain insights into dimer formation. To obtain a reliable structure prediction, we subjected this model to equilibration using molecular dynamics simulations.

Determination of the optimal tubulin isotype target as a method for the development of individualized cancer chemotherapy.

Background: As microtubules are essential for cell growth and division, its constituent protein β-tubulin has been a popular target for various treatments, including cancer chemotherapy. There are several isotypes of human β-tubulin and each type of cell expresses its characteristic distribution of these isotypes. Moreover, each tubulin-binding drug has its own distribution of binding affinities over the various isotypes, which further complicates identifying the optimal drug selection.

Modeling the yew tree tubulin and a comparison of its interaction with paclitaxel to human tubulin.

Purpose: To explore possible ways in which yew tree tubulin is naturally resistant to paclitaxel. While the yew produces a potent cytotoxin, paclitaxel, it is immune to paclitaxel's cytotoxic action.

Methods: Tubulin sequence data for plant species were obtained from Alberta 1000 Plants Initiative.

DNA repair inhibitors: the next major step to improve cancer therapy.

Modern cancer therapies, mainly ionizing radiation and certain classes of chemotherapies target DNA. Although these treatments disrupt the genome, their rationale is clear. They prevent cancer cells from dividing and proliferating.

Peloruside, laulimalide, and noscapine interactions with beta-tubulin.

This article reviews the recent findings regarding the binding sites, binding modes and binding affinities of three novel antimitotic drugs peloruside, laulimalide and noscapine with respect to tubulin as the target of their action. These natural compounds are shown to bind to β-tubulin and stabilize microtubules for the cases of peloruside A and laulimalide, and prolong the time spent in pause for noscapine. Particular attention is focused on β-tubulin isotypes as targets for new cancer chemotherapy agents and the amino acid differences in the binding site for these compounds between isotypes.

DNA Repair Inhibitors: Our Last Disposal to Improve Cancer Therapy.

Modern cancer therapies, mainly ionizing radiation and certain classes of chemotherapies target DNA. Although these treatments disrupt the genome, their rationale is clear. They prevent cancer cells from dividing and proliferating.

DNA polymerase beta (pol β) inhibitors: a comprehensive overview.

Base excision repair (BER) is the fundamental pathway responsible for the elimination of damaged DNA bases and repair of DNA single-strand breaks generated spontaneously or produced by DNA-damaging agents. Among the essential enzymes that are required to achieve the BER reaction is DNA polymerase beta (pol β), which has been regarded as a potential therapeutic target. More than 60 pol β-inhibitors have been identified so far; however, most of them are either not potent or not specific enough to become a drug.