Navigation Links
Supercomputer reveals new details behind drug-processing protein model

OAK RIDGE, Tenn. -- 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."

Contact: Morgan McCorkle
DOE/Oak Ridge National Laboratory

Related medicine news :

1. Harnessing the Web and supercomputers to track pathogens as they evolve
2. First large-scale study of pain reveals risk factors
3. Landmark survey reveals that most women who are done having children do not discuss their options with their OB/GYNs
4. Combined arterial imaging technology reveals both structural and metabolic details
5. Modern Technology Reveals Clues From Egyptian Mummy
6. Analysis reveals malaria, other diseases as ancient, adaptive and persistent foes
7. Study reveals details of alternative splicing circuitry that promotes cancers Warburg effect
8. The freshman 15 is just a myth, nationwide study reveals
9. Dopamine release in human brain tracked at microsecond timescale reveals decision-making
10. Blood vessel mapping reveals 4 new ZIP codes
11. Gene Mapping Reveals Clues to Bedbugs Pesticide Resistance
Post Your Comments:
Related Image:
Supercomputer reveals new details behind drug-processing protein model
(Date:10/13/2015)... , ... October 13, 2015 , ... The documentary ... Laemmle Music Hall in Beverly Hills October 2 - 8, coinciding with National Hereditary ... Award® consideration, the film takes us through the lives of women - and men ...
(Date:10/13/2015)... ... 13, 2015 , ... The added calories and sugar in an average trick-or-treat ... a parent to do? Registered dietitians from Retrofit , the leading corporate weight ... year. , “Halloween is a high-calorie holiday,” said Dara Aronow, Registered Dietitian, Retrofit. ...
(Date:10/13/2015)... WEST LAFAYETTE, Ind. (PRWEB) , ... October 13, ... ... to establish a new Pillars of Excellence in the Life Sciences Initiative aimed ... part of Purdue’s recently announced $2 billion “Ever True” capital campaign. , The ...
(Date:10/13/2015)... ... October 13, 2015 , ... Vision Group Holdings, the largest LASIK provider in ... brands including The LASIK Vision Institute and TLC Laser Eye Centers, Vision Group Holdings ... laser vision correction. , Global Laser Vision will continue to operate in San Diego ...
(Date:10/13/2015)... (PRWEB) , ... October 13, 2015 , ... ... enterprise focused on cancer patients, today announced a new partnership with the ... battling this rare type of non-Hodgkin’s lymphoma, their families and physicians. , ...
Breaking Medicine News(10 mins):
(Date:10/13/2015)... -- Synapse Biomedical Inc. ( ) reported today that ... use of the NeuRx ® Diaphragm Pacing System ... the United States and patient ... PAS study group met their initial enrollment goal ahead ... expanded the enrollment target to 150 participants.   ...
(Date:10/13/2015)... DUBLIN , Oct. 13 2015 ... addition of the "US & European markets ... report to their offering. --> ... "US & European markets for Meniscal Repair - ... --> Research and Markets ( ...
(Date:10/13/2015)... , Oct. 9, 2015 Research and Markets ... "Kombucha Market by Types (Bacteria, Yeast, Mold, Others), ... Mangoes, Flowers, Others), & by Region - Forecasts to ... --> --> The ... last few years. In terms of value, the market ...
Breaking Medicine Technology: