New Molecular Modeling Lab Key to Chemistry Research Work

by Tim Kaldahl

A new computer-based molecular modeling lab on the third floor of UNO's Durham Science Center has helped a pair of undergraduates win an American Chemical Society (ACS) Midwest region best poster competition this semester. The students – Teddy Woolman and Joshua Stopak – focused on an issue of human neurotransmission, and have made their chemistry professor, Haizhen (Andy) Zhong, very proud.

Zhong said the pair built more than 280 drug-like molecules and reported acetylcholinesterase (AChE) inhibitors with high-end computers and the state-of-the-art modeling software and carried out studies on docking all 280 molecules to AChE protein. Docking a small molecule to a protein is like finding a key for a lock. The key that turns on a lock must contain the complementary features of the lock. Similarly, a small molecule that inhibits a protein must contain structural features complementary to the binding pocket of a protein.

The work began last summer and looked at how the acetylcholinesterase (AChE), which is involved in Alzheimer's disease – might be inhibited by a small molecule. All of the research took place in a new computer lab. Last year, the space was used for storage.

"This kind of modeling is complementary to what could be physically tested in the future," Zhong said. "This testing of molecules helps researchers design better drug molecules targeting Alzheimer's disease and provides guidance in what researchers need to study further."

Computer modeling isn't a simple matter of inputting numbers and getting a quick result. Meticulous care is needed for the whole study. Testing a library of small molecules usually took half a day. Different kinds and types of measurement examined how well a molecule would fit into an AChE protein. Woolman and Stopak would put information in and then come back and analyze the results of the "docking study" the next day.

Student Teddy Woolman, a junior, said he spent about four hours each day in the lab during the summer. The effort was worth it, he said.

"These are the actual tools that an actual chemistry researcher would use," Woolman said.

Josua Stopak added that he has already seen job postings in pharmaceutical industry that are seeking individuals who have molecular computer modeling experience. Stopak is a senior who hopes to go on to medical school.

"It's a long way to go," Zhong said, before a real molecule could be created and tested in the real world. A third student of Zhong's, Sarah Norris, plans to continue the research on AChE inhibitors.

Woolman and Stopak will present their results at the end of the semester as part of their CHEM4950 class requirement. The title of the poster presentation was "Docking Studies of Acetylcholinesterase (AChE) Inhibitors." The Midwest ACS meeting took place in Iowa City, Iowa in late October.

"Having undergraduates do this level of research is extremely gratifying," said Harmon Maher, interim associate vice chancellor for Research and Creative Activity, "This work separates our students from others when they want to pursue graduate or professional schools. They already have demonstrated the level of commitment needed when doing top-notch research. The award help provides external recognition of the high quality of undergraduate research and educational opportunities that exist at UNO, and the students and their advisors are to be congratulated. "

In addition to Zhong and his students, Douglas Stack, another professor in chemistry said the computer-modeling lab has opened up a wealth of new research work for UNO students.

"This lab has been a great resource and it's being used a lot," he said. "It's been good for us."