PolyConstruct turns months of molecular modelling into a day’s work

Imagine trying to design a drug-delivery gel that safely carries medicine through the body and breaks down after it’s done its job — all without ever setting foot in a lab.

That’s what molecular simulation makes possible.

By modelling materials at the atomic level, scientists can test how they behave in different environments — like in the human body, under heat, or when exposed to chemicals — before they’re ever made in the lab.

This kind of simulation saves time and money, helps avoid dead ends, and accelerates the discovery of smarter, safer materials.

Now, a powerful new open-source tool, developed at the Australian Institute for Bioengineering and Nanotechnology (AIBN), is making that process dramatically faster and more accessible.

Led by Professor Megan O’Mara, the team behind PolyConstruct has transformed the once painstakingly manual task of setting up polymer simulations into a digitised process that takes just a day.

“We’re now able to explain much faster why a certain material might work better than another which is essential in areas like drug delivery or biodegradable plastics,” O’Mara said.

“That kind of insight used to take months of manual coding by someone with advanced skills. Now it’s accessible to researchers everywhere.”

From a long-term challenge to a game-changing toolkit

The project began nearly ten years ago when O’Mara was asked to simulate a polymer for gene therapy and discovered there was no tool to do it.

“There was no way to simulate biologically relevant polymers, which made it really hard for researchers to predict how new materials might work in real-world applications,” she said.

At the time, researchers had to build models atom by atom, define chemical rules manually, and write code line by line — what O’Mara describes as a ‘laborious’ process.

Her team then laid the groundwork, but the project took a leap forward when two PhD students — Rangika Munaweera and Ada Quinn — joined her group and tackled the final, critical challenges that turned the vision into reality.

Laying the Foundation

When he started his PhD in 2023, Munaweera soon realised that most tools available could only handle simple, linear structures, and not the complex, branched architectures often needed for biomedical materials.

“The tools just weren’t built to handle the kind of complex shapes we need for drug delivery,” he said.

“I adapted methods from protein modelling and built PolyBuild — a tool that lets you define a polymer’s blueprint or connection map and automatically generate parameters that are ready for simulation.”

His work became the first building block of PolyConstruct, enabling researchers to design more advanced and functional polymers from the ground up.

Capturing the Chemistry

Once a computer model of the polymer is built, it still needs chemical rules applied so researchers can see how it moves and behaves.

That’s where the second building block, PolyTop, comes in — written by Richard Morris, a former student of O’Mara at ANU, and current O’Mara Group honours student Luna Morrow.

“PolyTop was built to handle the underlying chemistry. It defines how the atoms are connected and interact, so the simulation reflects how the material behaves, not just what it looks like,” Professor O’Mara said.

This step is essential for testing whether a polymer could function in a real-world setting like carrying a drug through the body or breaking down safely after use.

Cracking the shape challenge

While PolyBuild and PolyTop generated the structure and chemistry of a polymer, PhD researcher Ada Quinn quickly realised the ability to define its actual 3D shape was still missing.

“I had the structure from PolyBuild, and the chemistry from PolyTop, but the shape couldn’t be defined in a way the simulation engine could use,” she said.

“I realised we needed to generate structural coordinate so the simulation engine could read the polymer’s shape correctly.

“Without that, the simulation would fail or behave unrealistically.

“These polymers were just too random and complex for existing tools to handle.”

To bridge that gap, Quinn built a new tool from scratch — PolyConf — that could generate accurate spatial coordinates and feed them into the simulation engine.

Her work solved one of the most common bottlenecks in polymer modelling and was the final piece of the puzzle to complete the full PolyConstruct suite.

Making advanced science more accessible

Beyond speed and precision, PolyConstruct opens high-level materials discovery to a much broader group of researchers, with labs around the world using it to explore materials for medical, environmental and industrial use.

“This isn’t just about researchers doing the same work faster,” said Quinn.

“It’s allowing us to ask new questions we couldn’t previously explore outside of the lab — like how a polymer folds, degrades, or responds to heat and light.

“That kind of insight is critical to designing materials that are safer, smarter and more sustainable.”

This paper was published in the Journal of Chemical Information and Modeling on 17 March 2025 and was co-authored by Rangika Munaweera, Ada Quinn, Luna Morrow, Richard A. Morris from the Australian National University, and Megan L. O’Mara.

PolyConstruct is available via GitHub: GitHub - OMaraLab/polyconstruct: A Python library for constructing polymer topologies and coordinates