Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Supercomputer reveals new details behind drug-processing protein model

07.12.2011
Supercomputer simulations at the Department of Energy's Oak Ridge National Laboratory are giving scientists unprecedented access to a key class of proteins involved in drug detoxification.

Jerome Baudry and Yinglong Miao, who are jointly affiliated with ORNL and the University of Tennessee, have performed simulations to observe the motions of water molecules in a class of enzymes called P450s. Certain types of P450 are responsible for processing a large fraction of drugs taken by humans.

The supercomputer simulations were designed to help interpret ongoing neutron experiments.

"We simulated what happens in this enzyme over a time scale of 0.3 microseconds, which sounds very fast, but from a scientific point of view, it's a relatively long time," Baudry said. "A lot of things happen at this scale that had never been seen before. It's a computational tour de force to be able to follow that many water molecules for that long."

The team's study of the water molecules' movements contributes to a broader understanding of drug processing by P450 enzymes. Because some populations have a slightly different version of the enzymes, scientists hypothesize that mutations could partially explain why people respond differently to the same drug. One possibility is that the mutations might shut down the channels that bring water molecules in and out of the enzyme's active site, where the chemical modification of drugs takes place. This could be investigated by using the computational tools developed for this research.

By simulating how water molecules move in and out of the protein's centrally located active site, the team clarified an apparent contradiction between experimental evidence and theory that had previously puzzled researchers. X-ray crystallography, which provides a static snapshot of the protein, had shown only six water molecules present in the active site, whereas experimental observations indicated a higher number of water molecules would be present in the enzyme.

"We found that even though there can be many water molecules -- up to 12 at a given time that get in and out very quickly -- if you look at the average, those water molecules prefer to be at a certain location that corresponds to what you see in the crystal structure," Miao said. "It's a very dynamic hydration process that we are exploring with a combination of neutron scattering experiments and simulation."

The simulation research is published in Biophysical Journal as "Active-Site Hydration and Water Diffusion in Cytochrome P450cam: A Highly Dynamic Process."

The team was supported by an Experimental Program to Stimulate Competitive Research (EPSCOR) grant from the DOE Office of Science and funding from the University of Tennessee. Computing time on the Kraken supercomputer was supported by a National Science Foundation TeraGrid award.

ORNL is managed by UT-Battelle for the Department of Energy's Office of Science.

Morgan McCorkle | EurekAlert!
Further information:
http://www.ornl.gov

More articles from Life Sciences:

nachricht The world's tiniest first responders
21.06.2018 | University of Southern California

nachricht A new toxin in Cholera bacteria discovered by scientists in Umeå
21.06.2018 | Schwedischer Forschungsrat - The Swedish Research Council

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Better model of water under extreme conditions could aid understanding of Earth's mantle

21.06.2018 | Earth Sciences

What are the effects of coral reef marine protected areas?

21.06.2018 | Life Sciences

The Janus head of the South Asian monsoon

21.06.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>