Scientists develop a more effective molecular modeling process

Sep 26, 2013

It's difficult and time-consuming to produce accurate computer models of molecules, primarily because traditional modeling methods are limited in their ability to handle alternative molecular shapes and, consequently, are subject to multiple errors.

Moreover, the traditional approach uses or algorithms that are run sequentially, refining the structural details of the model with each separate algorithm—a method that has been revolutionized by personal computing, but still requires labor-intensive for .

A new method developed by scientists on the Florida campus of The Scripps Research Institute (TSRI) takes another tack entirely, combining existing formulas in a kind of algorithmic stew to gain a better picture of molecular structural diversity that is then used to eliminate errors and improve the final model.

The method was described in a paper published online ahead of print on September 26, 2013 by the journal Structure.

The new process, called Extensive Combinatorial Refinement (ExCoR), could help improve the development of that depend to a great degree on detailed to determine how they work against specific disease targets.

"Our combinatorial method creates computerized molecular models in a more automated way," said Kendall Nettles, a TSRI associate professor who led the study. "This is an important component of —to do them in a more automated fashion will significantly help the process."

Improvement and Some Surprises

In the study, the scientists subjected more than 50 to 256 distinct combinations of algorithms and refinement factors that eventually totaled more than 12,000 independent refinement runs.

Nettles and his colleagues measured the improvement in the models by what is known as the R-factor, which measures the similarity between the actual structure of the molecule and the —in other words, just how closely the refined structure model can predict the factual data.

"Lowering that R-factor is the goal—that's the selection process for finding the best algorithms," Nettles said.

While the study found that no single algorithm consistently produced the best model, the scientists did find some surprises.

"Some algorithms, if you combine them, tend to work better at producing a refined model," said Research Associate Jerome C. Nwachukwu, the first author of the study. "What we didn't expect was two algorithms that worked separately but didn't work in combination."

It is this strange overlap makes it impossible to predict which combinations of algorithms will work best for an individual structure.

"The refinement effects of the various algorithms depend on the structure itself," Nwachukwu said.

Explore further: New analysis shows how proteins shift into working mode

More information: "Improved Crystallographic Structures using Extensive Combinatorial Refinement," will appear in the November 5, 2013 print issue of Structure, 2013.

add to favorites email to friend print save as pdf

Related Stories

New analysis shows how proteins shift into working mode

Aug 09, 2013

In an advance that will help scientists design and engineer proteins, a team including researchers from SLAC and Stanford has found a way to identify how protein molecules flex into specific atomic arrangements ...

Visualizing the structures of molecules

Dec 05, 2012

Hitoshi Goto and colleagues have developed high performance molecular simulation tools to study the 3D arrangement of molecules, enabling better design of medicinal and agricultural drugs which are more effective ...

Recommended for you

Illuminating the dark side of the genome

2 hours ago

Almost 50 percent of our genome is made up of highly repetitive DNA, which makes it very difficult to be analysed. In fact, repeats are discarded in most genome-wide studies and thus, insights into this part ...

Fighting bacteria—with viruses

Jul 24, 2014

Research published today in PLOS Pathogens reveals how viruses called bacteriophages destroy the bacterium Clostridium difficile (C. diff), which is becoming a serious problem in hospitals and healthcare institutes, due to its re ...

Atomic structure of key muscle component revealed

Jul 24, 2014

Actin is the most abundant protein in the body, and when you look more closely at its fundamental role in life, it's easy to see why. It is the basis of most movement in the body, and all cells and components ...

Brand new technology detects probiotic organisms in food

Jul 23, 2014

In the food industr, ity is very important to ensure the quality and safety of products consumed by the population to improve their properties and reduce foodborne illness. Therefore, a team of Mexican researchers ...

User comments : 0