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Primeur weekly 2013-01-21

The Cloud

HP helps service provider ITX Enterprises expand private Cloud service delivery ...

IBM and the Australian Open mark 20 years of serving a winning advantage to tennis fans ...

Ho Chi Minh City University of Information Technology selects IBM PureSystems ...

Oracle delivers Oracle Infrastructure as a Service on Premise with Capacity on Demand ...

Clouds for Savings, Clouds for Quality - Governments leading by example at Cloudscape V ...

EuroFlash

German meteorological service DWD awards $23 million contract to Cray ...

Adaptive Computing to work with Cray to manage computing workloads for the North-German Supercomputing Alliance (HLRN) ...

PRACE Summer of HPC ...

Altair's HyperWorks Partner Alliance expands its scope with the addition of NovaCast Systems to its software line-up ...

Altair releases PBS Professional 12.0, with 40 percent faster scheduling, innovative utilization features and additional plug-ins for execution events ...

Computational methods reveal how hospital-acquired bacteria spread ...

A new dimension in mobile telecommunications ...

Sauber F1 Team fuels chase for podium finishes with NetApp storage foundation ...

Mathematical breakthrough sets out rules for more effective teleportation ...

Bright Cluster Manager speeds Chinese climate change research efforts ...

USFlash

Asia Student Supercomputer Challenge 2013 to issue Call for Participation ...

Chaotic spin vortices could lead to new computer memories ...

2013 IEEE International Conference on Big Data to issue Call for Workshop Proposals ...

Intel and Facebook collaborate on future data centre rack technologies ...

UC Riverside nanotechnologists help launch new national centre devoted to micro-electronics ...

NETL's new supercomputer ranks among the world's Top 100 ...

Notre Dame to be part of $194 million university research centre network ...

Coles Supermarkets revamps data warehouse system with Oracle ...

FAIR Health selects Oracle Exadata Database Machine and Oracle's Sun ZFS storage appliance ...

Oracle's consolidated data warehouse system helps Turkcell accelerate reporting, and save on storage and energy costs ...

Simon Fraser University materials and particle science attract government funding ...

Researchers at Mount Sinai School of Medicine use TACC supercomputers to simulate the organisation of membrane proteins at the cell surface ...

Researchers at Mount Sinai School of Medicine use TACC supercomputers to simulate the organisation of membrane proteins at the cell surface

21 Jan 2013 Austin - The last time you popped a pill for a headache or a stuffy nose, did you think about how the medication actually alleviates your pain or unblocks your stuffy nose? Curing a disease is a complex process and involves understanding how various proteins found on the surface of human body cells convert external stimuli into intracellular biological signals.

Cell signaling intrigues Dr. Marta Filizola, an associate professor of Structural and Chemical Biology at Mount Sinai School of Medicine in New York. Her laboratory work is focused on understanding signal transduction processes mediated by certain cell surface membrane proteins called G protein-coupled receptors, which interact with about half of all drugs currently on the market. Important insights into how these proteins work at a molecular level earned the scientists who contributed to them the Nobel Prize in Chemistry in 2012.

"Membrane proteins are protein molecules embedded in the cell membrane surface", Dr. Filizola stated. "They play a major role in mediating the effect of drugs."

G protein-coupled receptors are important molecular machines since they respond to a variety of stimuli, including the chemicals in a drug. "They interact with various agents, change form, and translate the information about these chemicals into a biological signal in the interior of the cell", Dr. Filizola stated. By doing this they help the drug exert its function on disease states.

Without G protein-coupled receptors, medicines would not be effective because they would not know their way into the cell. Yet the exact workings of the G protein-coupled receptors at the molecular level are still shrouded in mystery. There is a huge amount of debate as to what exact parts of these proteins are important and how other aspects, like their ability to assemble (or oligomerize) in the cell surface membrane, affect cell signaling.

The Filizola lab runs computer simulations of oligomeric assemblies of G protein-coupled receptors on the supercomputers at the Texas Advanced Computing Center (TACC), trying to answer questions like: How do drugs affect the spatio-temporal organization of G protein-coupled receptors in the cell membrane?

"G protein-coupled receptors have been reported to form oligomeric complexes in a variety of disease states", she stated. "I'm trying to find out how these protein complexes process cell signaling so that we can make drugs more specific and design more efficient medicines."

Understanding how opioid receptors work is an important aspect of research in the Filizola lab. Opioid receptors are a group of G protein-coupled receptors that respond to opioids - medications commonly used to relieve pain. Their latest simulations are aimed at comprehending the fundamental mechanisms of the opioid receptor function. The Filizola lab creates movies from the simulations that reveal the way proteins - which are never static - interact with drug molecules and other proteins. These ‘movies' help identify the factors that contribute to a molecular-level understanding of the mechanism of action of drugs at individual or oligomeric receptors. This information is used to create more efficient medications or to stop unpleasant side effects.

In a recently published paper inPLoS Computational Biology, the Filizola lab examined how different drugs can change the shape of a prototypic G protein-coupled receptor, thus producing different biological responses. In another paper, also inPLoS Computational Biology, they present a methodology to estimate how strong interactions between G protein-coupled receptors can be.

"Interactions between receptors can be quite dynamic in nature", Dr. Filizola stated. Understanding how drugs bind to a G protein-coupled receptor and the changes this binding induce to the receptor may help researchers discriminate those causative elements that stimulate the side effects.

She is hoping that the results of her simulations will help formulate new hypotheses on how drugs and protein receptors function so one can work on creating effective drugs with minimal side effects.

"Side effects are an important issue", Dr. Filizola stated. "We can develop the best pain curing medication ever, but if it causes an addiction then how good is it really?"

The technical issues involved in this kind of research are tough. She uses the Ranger supercomputer extensively in her work, in addition to the Scientific Computing Facility at Mount Sinai, but points out the limitations of simulations.

"We have to observe the movements of the proteins for a long time", she stated. "Models here are only approximations and the simulations involved are complex. It's easy to miss out on important aspects of the interactions even though now we have access to more detailed structural information about G protein-coupled receptors and resources like those of TACC to help the computations necessary. These aren't simulations you can run on your desktop."

In the future Dr. Filizola plans to extend her molecular dynamics simulations to even larger supramolecular complexes to understand cell signaling better.

"Safer and effective drugs are a pressing need and we must address the complexities involved fast."
Source: Texas Advanced Computing Center - TACC

Back to Table of contents

Primeur weekly 2013-01-21

The Cloud

HP helps service provider ITX Enterprises expand private Cloud service delivery ...

IBM and the Australian Open mark 20 years of serving a winning advantage to tennis fans ...

Ho Chi Minh City University of Information Technology selects IBM PureSystems ...

Oracle delivers Oracle Infrastructure as a Service on Premise with Capacity on Demand ...

Clouds for Savings, Clouds for Quality - Governments leading by example at Cloudscape V ...

EuroFlash

German meteorological service DWD awards $23 million contract to Cray ...

Adaptive Computing to work with Cray to manage computing workloads for the North-German Supercomputing Alliance (HLRN) ...

PRACE Summer of HPC ...

Altair's HyperWorks Partner Alliance expands its scope with the addition of NovaCast Systems to its software line-up ...

Altair releases PBS Professional 12.0, with 40 percent faster scheduling, innovative utilization features and additional plug-ins for execution events ...

Computational methods reveal how hospital-acquired bacteria spread ...

A new dimension in mobile telecommunications ...

Sauber F1 Team fuels chase for podium finishes with NetApp storage foundation ...

Mathematical breakthrough sets out rules for more effective teleportation ...

Bright Cluster Manager speeds Chinese climate change research efforts ...

USFlash

Asia Student Supercomputer Challenge 2013 to issue Call for Participation ...

Chaotic spin vortices could lead to new computer memories ...

2013 IEEE International Conference on Big Data to issue Call for Workshop Proposals ...

Intel and Facebook collaborate on future data centre rack technologies ...

UC Riverside nanotechnologists help launch new national centre devoted to micro-electronics ...

NETL's new supercomputer ranks among the world's Top 100 ...

Notre Dame to be part of $194 million university research centre network ...

Coles Supermarkets revamps data warehouse system with Oracle ...

FAIR Health selects Oracle Exadata Database Machine and Oracle's Sun ZFS storage appliance ...

Oracle's consolidated data warehouse system helps Turkcell accelerate reporting, and save on storage and energy costs ...

Simon Fraser University materials and particle science attract government funding ...

Researchers at Mount Sinai School of Medicine use TACC supercomputers to simulate the organisation of membrane proteins at the cell surface ...