Modulation of Human Hsp90α Conformational Dynamics by Allosteric Ligand Interaction at the C-Terminal Domain.

Recent years have seen heat shock protein 90 kDa (Hsp90) attract significant interest as a viable drug target, particularly for cancer. To date, designed inhibitors that target the ATPase domain demonstrate potent anti-proliferative effects, but have failed clinical trials due to high levels of associated toxicity. To circumvent this, the focus has shifted away from the ATPase domain.

Allosteric Modulation of Human Hsp90α Conformational Dynamics.

Central to Hsp90's biological function is its ability to interconvert between various conformational states. Drug targeting of Hsp90's regulatory mechanisms, including its modulation by cochaperone association, presents as an attractive therapeutic strategy for Hsp90 associated pathologies. In this study, we utilized homology modeling techniques to calculate full-length structures of human Hsp90α in closed and partially open conformations and used these structures as a basis for several molecular dynamics based analyses aimed at elucidating allosteric mechanisms and modulation sites in human Hsp90α.

MD-TASK: a software suite for analyzing molecular dynamics trajectories.

Summary: Molecular dynamics (MD) determines the physical motions of atoms of a biological macromolecule in a cell-like environment and is an important method in structural bioinformatics. Traditionally, measurements such as root mean square deviation, root mean square fluctuation, radius of gyration, and various energy measures have been used to analyze MD simulations. Here, we present MD-TASK, a novel software suite that employs graph theory techniques, perturbation response scanning, and dynamic cross-correlation to provide unique ways for analyzing MD trajectories.

Perturbation-Response Scanning Reveals Key Residues for Allosteric Control in Hsp70.

Hsp70 molecular chaperones play an important role in maintaining cellular homeostasis, and are implicated in a wide array of cellular processes, including protein recovery from aggregates, cross-membrane protein translocation, and protein biogenesis. Hsp70 consists of two domains, a nucleotide binding domain (NBD) and a substrate binding domain (SBD), each of which communicates via an allosteric mechanism such that the protein interconverts between two functional states, an ATP-bound open conformation and an ADP-bound closed conformation. The exact mechanism for interstate conversion is not as yet fully understood.

Binding and entry of a non-enveloped T=4 insect RNA virus is triggered by alkaline pH.

Tetraviruses are small, non-enveloped, RNA viruses that exclusively infect lepidopteran insects. Their particles comprise 240 copies of a single capsid protein precursor (CP), which undergoes autoproteolytic cleavage during maturation. The molecular mechanisms of capsid assembly and maturation are well understood, but little is known about the viral infectious lifecycle due to a lack of tissue culture cell lines that are susceptible to tetravirus infection.

Crosstalk analysis of ring resonator switches for all-optical routing.

Optical switches based on ring resonator cavities were fabricated by a silicon photonics foundry process and analyzed for optical crosstalk at various data rates and channel spacings. These devices were compared to commercial bandpass filters and at 20Gb/s, 0.5dB power penalty is observed due to spectral filtering for bit error ratio threshold of 1 × 10.

Human, vector and parasite Hsp90 proteins: A comparative bioinformatics analysis.

The treatment of protozoan parasitic diseases is challenging, and thus identification and analysis of new drug targets is important. Parasites survive within host organisms, and some need intermediate hosts to complete their life cycle. Changing host environment puts stress on parasites, and often adaptation is accompanied by the expression of large amounts of heat shock proteins (Hsps).

JMS: An Open Source Workflow Management System and Web-Based Cluster Front-End for High Performance Computing.

Complex computational pipelines are becoming a staple of modern scientific research. Often these pipelines are resource intensive and require days of computing time. In such cases, it makes sense to run them over high performance computing (HPC) clusters where they can take advantage of the aggregated resources of many powerful computers.

SANCDB: a South African natural compound database.

Background: Natural products (NPs) are important to the drug discovery process. NP research efforts are expanding world-wide and South Africa is no exception to this. While freely-accessible small molecule databases, containing compounds isolated from indigenous sources, have been established in a number of other countries, there is currently no such online database in South Africa.