Research Spotlight:
Dr. Albert Lau
Dr. Albert Lau is an Associate Professor of biophysics and biophysical chemistry at the Johns Hopkins School of Medicine.
His research combines computational and experimental approaches to study the atomic and molecular details of protein complexes crucial for intercellular communication, with a focus on ionotropic glutamate receptors (iGluRs).
Q: What is the focus of your research?
AL: “Our focus revolves around using computational methods to try to understand how biological macromolecular machines work at the atomic and molecular level. These machines include proteins, protein-nucleic acids, and complexes of proteins and nucleic acids. Additionally, we are involved in some areas of computer-aided drug design.”
Q: How do computational and experimental approaches complement each other in your research?
AL: “Generally, it can happen in two ways. Sometimes, conducting experiments yields results or observations that are challenging to explain. In such cases, we can carry out computer simulations to aid in the interpretation of these results. Conversely, our simulations sometimes generate hypotheses that can be tested experimentally.”
Q: What led you to focus on ionotropic glutamate receptors (iGluRs) in your studies?
AL: “I started studying iGluRs as a postdoctoral scholar at the University of Chicago because I was interested in brain function and how neurons communicate with each other. When I joined the faculty here at Hopkins School of Medicine I continued to study these neuroreceptors expanding on the questions I wanted to ask.”
Q: What is the significance of iGluRs in synaptic plasticity and its role in learning and memory?
AL: “IGluRs mediate most of the excitatory synaptic communication in the brain. The molecular basis for learning and memory is partly due to how strongly groups of neurons communicate, where iGluRs play a significant role.”
Q: What specific computational methods in molecular simulation and statistical thermodynamics do you use in your research?
AL: “We employ molecular dynamics simulations, which involve integrating equations of motion to simulate the dynamics of atoms in a molecule. We conduct a specific type of simulation called free energy calculations to determine the free energies and other thermodynamic properties of our systems. We also use machine-learning approaches to discover potential drug-binding sites on proteins.”
Q: How has computation changed the way we study protein complexes and intercellular communication?
AL: “In functional experiments, you can observe the results of biochemical processes but not the atomic-level details. There are experiments in structural biology where you can map out the chemical structure of macromolecules and see the atomic level details. However, these experiments provide snapshots of dynamic processes, like a high-resolution freeze frame picture of a dynamic process. Computational methods allow us to use physics to simulate what is happening in these biochemical processes and understand the motions of proteins and other small molecules. Thus, they complement structural snapshots by adding dynamics.”
Q: What are the next steps or future directions for your research?
AL: “We’re continuing to study iGluRs, broadening the scope of the questions we want to ask. Initially, our focus was on understanding the specific functions of the parts of these receptors. We’re now expanding our scope to larger parts of these receptors. Moreover, we are looking at the different systems through collaborations with my colleagues at Johns Hopkins. We’re examining protein complexes involved in bacterial cell division. In human systems, we focus on protein complexes that help untangle DNA when replicated during cell division. Additionally, we are looking at proteins involved in the immune response and trying to understand how they recognize and bind to each other as part of how they function.”
Q: What is the impact or value of Rockfish in your research?
AL: “Rockfish plays a critical role in our research, serving as our primary computational resource. It gives us access to CPUs and GPUs that would be otherwise difficult to afford. The flexibility of Rockfish allows us to carry out simulations and calculations that would be unfeasible on other resources.”
Learn more about Lau Lab and their work here