Research Projects in Yasmin Binti Shamsudin Group
We use computer-based modeling and simulations to elucidate the molecular mechanisms and interactions between ligands and protein that drive binding, inhibition, and catalysis. You can read more about our ongoing research projects below.
Beta-lactamases, antibiotics, and inhibitors
Antibiotic resistance is one of the biggest health problems in the world. In 2019, almost 1.3 million people died due to antibiotic resistant bacterial infections. Unfortunately, the development of new antibiotics is slow.
One of the causes of antibiotic resistance is beta-lactamases, enzymes that break down antibiotics. We study how the structures of beta-lactamases have changed during their evolution and how this affects their dynamics and function. We are also interested in understanding how structural elements and functional groups in antibiotics and beta-lactamase inhibitors affect binding and functionality in different classes of beta-lactamases.
Electric fields and catalysis in biomolecules
Electric fields are one of the driving forces in enzymatic catalysis. Through a combined experimental and computer-based method, it is possible to calculate electric fields projected on a functional group. We strive to develop a new completely computer-based method for accurately predicting electric fields in biological systems. In collaboration with an experimental group, we look at how targeted mutations in enzymes affect their dynamics and interactions with ligands. The goal is to see if we can predict and explain the differences in behavior and catalytic rates of enzymes.
By traditional protein design, large amounts of proteins are created through random mutations. As most new proteins do not show any improvement, they are discarded, leading to unnecessary chemical and biological waste. The few proteins that show potential are retained and undergo new mutations until they are considered optimized. Although one can find improved proteins through this process, it does not increase our understanding of key properties for improving the protein.
Through modeling and computer simulations, we can get an idea of how proteins behave over time and how they interact with other molecules. Our partners perform higher theoretical calculations or molecular biological and biophysical-chemical experiments to validate our models and test our predictions. With validated models, we can make more reliable predictions about how similar proteins will behave and this can lead to cheaper, faster, and more environmentally friendly design of new proteins with specific functionality that can be used in medicine and biotechnology.