Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Computer method identifies potentially active enzymes


Better drugs, improved industrial applications and even cleaner laundry may be possible with a new computer method to predict which hybrid enzymes are likely to have high activity, according to a team of Penn State chemists and chemical engineers.

"FamClash is quite successful at qualitatively predicting the pattern of the specific activity of the hybrids," the researchers report in this week’s online issue of the Proceedings of the National Academy of Sciences. "By identifying incompatible residue pairs in the hybrids, this method provides valuable insights for protein engineering interventions to remedy these clashes," the researchers say. FamClash is a computer method used to predict which hybrid enzymes are likely to have activity and which are not. Hybrid enzymes form when researchers combine similar enzymes from two or more different organisms. The variant enzymes are broken and recombined with parts from the original enzymes creating the new one.

"We have worked out ways to make libraries of novel enzymes by splicing proteins together," says Alexander R. Horswill, postdoctoral fellow in chemistry. "We wanted to know how active the new enzymes would be compared to the wild type."

Industrial processes use enzymes when reactions are too slow or too expensive to carry out without a catalytic boost. The most familiar use of enzymes is in laundry detergents where dirt-removing enzymes can gobble up stains even in cold water.

" It is hard to create an enzyme that is better than what occurs in nature," says Horswill. "But the FamClash approach will aid in engineering enzymes to work better in unnatural conditions, such as low or high temperatures, basic or acidic environments or organic solvents."

Horswill and Stephen J. Benkovic, the University professor, the Evan Pugh Professor of Chemistry and holder of the Eberly Chair in Chemistry, used enzymes from Escherichia coli and Bacillus subtilis, two common bacteria. Both produce forms of dihydrofolate reductases or DHFR that are 44 percent identical at the protein level. ITCHY or incremental truncation for the creation of hybrid enzymes was used to splice these DHFR enzymes together. Libraries of new and potentially interesting enzymes were created, but these new proteins do not necessarily have any enzymatic activity and therefore many of them were tested in the laboratory for activity. Working on the computer, rather than in the laboratory, Manish C. Saraf, graduate student in chemical engineering and Costas D. Maranas, associate professor of chemical engineering developed FamClash to understand and predict which combinations of pieces from the original enzymes would cause clashes and diminish activity and which will form active hybrid enzymes.

"First we have the computer program generate all the hybrids that could form using ITCHY," says Saraf. "Then we look at every residue combination in each hybrid for pair clashes."

To function properly, protein strands need to fold in a specific way so that certain domains are next to or aligned with other domains. Both forms of enzymes studies here have similar structure and function, however, clashes occur in hybrids when they retain fragments from original enzymes that are not compatible with each other.

"Pairs of residues that are too big, or too small, or have the wrong electrical charge can cause these clashes that prevent these hybrids from folding correctly," says Saraf. "We hypothesize that the greater the number of clashes that exist in the hybrids, the less likely it is to fold correctly and therefore lower activity will be present."

The hybrid combinations are then ranked for predicted enzyme activity based on the number of clashes present. "It is very helpful to experimentalists to know where introduced crossovers will produce high activity," says Horswill. "The long-term goal is to engineer enzymes for specific functions."

This engineering might come about by altering the residues so that clashes no longer exist. At this point, the researchers consider all clashes equal in reducing activity, but this is not necessarily true. Some clashes may be much more damaging than others.

"Now we assume that more clashes are worse, but we do not really know that," says Saraf. "We want to see what happens if we eliminate all clashes. Will it have equal activity? We are hoping that will tell us which predictions are right and which are wrong. "

The researchers have also tried the approach on other enzyme systems and observed similar trends in prediction.

The National Science Foundation and the National Institutes of Health supported this research.

A’ndrea Elyse Messer | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Ice shelf vibrations cause unusual waves in Antarctic atmosphere

25.10.2016 | Earth Sciences

Fluorescent holography: Upending the world of biological imaging

25.10.2016 | Power and Electrical Engineering

Etching Microstructures with Lasers

25.10.2016 | Process Engineering

More VideoLinks >>>