A new imaging method, called Transient Induced Molecular Electronic Spectroscopy (TIMES), allows researchers to investigate protein-ligand interactions without introducing disturbances to their binding. Researchers used Stampede to provide insights into how TIMES works. (Credit: Tiantian Zhang, Tao Wei, Yuanyuan Han, Heng Ma, Mohammadreza Samieegohar, Ping-Wei Chen, Ian Lian, and Yu-Hwa Lo)
Things that occur on the surface are frequently given short shrift when compared to what occurs on inside. However, with chemical reactions, what happens on the surface can mean the difference between a working material and one that refuses to carry out its duty.
Tao Wei, an assistant professor of Chemical Engineering at Lamar University, is involved n the study of surface - also called as "interfacial" - phenomena as a way to develop and enhance bio-nano technologies and functional materials.
By understanding the quantum and atomic mechanisms of interfacial chemistry and physics, he is helping to advance biosensors that can accelerate drug development, design better materials for desalinization, and develop new ways of producing energy from bacteria.
High Performance Research
To analyze the properties of bio- and nano-materials, Wei uses simulations that rely on parallel computing clusters such as the Stampede supercomputer at the
Texas Advanced Computing Center (TACC), one of the world’s fastest academic systems.
Computer simulations have become an important tool to complement experimental research in the development of nano-materials and bio-technologies. Simulations provide atomistic details and illustrate quantum processes, which are difficult to detect in experiments.
Tao Wei, Assistant Professor, Lamar University
Arieh Warshel, Michael Levitt and Martin Karplus won the 2013 Nobel Prize in Chemistry for the development of multi-scale models of complex chemical systems, reinforcing the significance of computational simulations in chemistry.
In fields spanning from drug development to energy production, these techniques have become very useful.
Since starting his research group at Lamar University three years ago, Wei has used computational simulations at TACC to publish seven papers and to make 18 conference presentations.
"TACC gives my new research group extraordinary help," Wei said.
From 2014 to 2016, the National Science Foundation-funded Extreme Science and Engineering Discovery Environment (XSEDE) program awarded Wei's group many million computing hours on Stampede. He also uses many other supercomputers - including the Department of Energy-funded Titan and Mira systems and the NSF-supported Gordon and SuperMIC systems - to make progress on a number of crucial problems.
By using large-scale parallel computations on parallel computer clusters such as Stampede, we have been able to study the biological systems such as protein adsorption, electron transfer and lipid packing, and to design functional materials and biotechnologies.
Tao Wei, Assistant Professor, Lamar University
The TIMES They Are A-Changin'…
Ligands are small molecules that stick to biomolecules, including proteins. They are frequently used in pharmacology and biochemistry to control a protein's structure or to signal alterations in the protein environment.
Researchers have often used techniques such as crystallization and fluorescent labeling to examine how exactly ligands and proteins interact. However, these techniques either change the conditions of the reaction or hinder what can be studied.
Working with partners from Lamar University and the University of California San Diego, Wei and his team helped to create a new technique to examine protein-ligand interaction, called Transient Induced Molecular Electronic Spectroscopy (TIMES).
The benefit of the technique is that it can characterize protein-ligand interactions without causing disturbances to their binding.
With TIMES, ligands, proteins, and protein-ligand complexes move through an aqueous medium and interact with an electrode surface. Detectors connected to a low-noise electric amplifier generate signals that display the polarized electric response of the reaction products as they near the electrode surface.
These can be tested to establish exactly how the ligands and proteins bind - to what extent, in what orientation, and over what timescale.
In October, the team showed the accuracy of the TIMES method by measuring the protein and ligand interactions between lysozyme - an enzyme that damages bacterial cell walls - and the N-acetyl-D-glucosamine (NAG) ligand and its trimer, NAG3. The research was published in the ACS Central Science journal.
The approach of computational physics has provided extremely valuable information and insight. Computational physics plays a far greater role than mere modeling of the process microscopically. It is a valuable approach to help us conceive hypotheses that are testable experimentally, making the discovery process more productive and rational.
Yu-Hwa Lo, Professor, University of California at San Diego
Protein–ligand interactions are a subject of immense interest in the biochemical field because of their practical applications in drug discovery.
The research was supported by multiple grants from the National Science Foundation (Grant ECCS-1610516) and by Vertex Pharmaceuticals, Inc.
Peering into Nano-Pores
Polyamides are the most extensively used material to desalinate and purify surface water, seawater, and wastewater using a process called membrane-based reverse-osmosis.
"It's a very mature material," Wei said. "But we need to increase water permeation without losing desalination to lower the energy costs."
To improve the separation capabilities of the material, which could lead to important commercial and societal benefits, it is vital to understand the microscopic structure of the polyamide membrane and the molecular transfer process at the atomic level.
Polyamide membranes are very thin, just 100 nm wide, and the pore size through which ions pass is just .3 nm, making it hard to establish experimentally what factors could be changed to enhance the performance of the material.
"It's very important that we have a tool to investigate the microstructure and molecular transfer through nanoporous membranes to see what's going on inside," he said.
In a research paper in the Journal of Physical Chemistry B in September 2016, Wei and his team, collaborating with Shroll Murad, Chair of Chemical and Biological Engineering at the Illinois Institute of Technology, illustrated an attempt to use simulations to distinguish local structures in the material that are believed to be responsible for its macro-scale behavior.
Performing a series of virtual experiments on Stampede, they discovered that the extent to which benzene rings in the material were cross-linked – held together not just at the ends, but also in the middle – played a key role in the transfer of water.
Water can permeate through the ring faster along certain paths, and those monomers are not cross-linked very well.
Tao Wei, Assistant Professor, Lamar University
A bottom-up approach was used, where they derived the parameters of the materials exclusively from the physics of the materials and their molecular bonding. The team discovered that the material’s characteristics, including its pore size distributions, density, water diffusion and salt exclusion, matched with results from experimentally synthesized membranes and former simulation studies.
In a follow-on study, Wei is studying the incorporation of nano-materials such as graphene and carbon nanotubes into pure polymer membranes to observe if they enhance water permeation.
"A better understanding of the structure of polyamide membranes will help design future desalinization and filtration methods, which will lower the energy costs and provide a lot of economic benefits," he said.
The research was supported by grants from the National Science Foundation, the National Basic Research Program of China, the National Natural Science Foundation of China and the Center of Air and Water Quality at Lamar University.
Exploring Electricity-Producing Bacteria
A third computational project on Stampede guided by Wei, explores the electrical properties of a unique type of bacteria that can harness energy from its environment through the cycling of sulfur, nitrogen, and iron.
Understanding the actions of the bacterial proteins that enable this process - called as multiheme cytochromes - can help in numerous applications, including solar-conversion catalysts, bioenergy production, and the elimination of toxic hexavalent chromium from water.
However, the structure of the bacterial proteins is not well-known.
"We know that this type of bacteria can transfer electrons from inside to outside through certain protein nano-wires," Wei said. "But we don't know their complete protein structure and we don't know how those proteins pack to form a nanowire."
To collect these details and to understand the way the proteins transfer electrons, Wei uses molecular dynamics simulations, where molecules and atoms are allowed to interact for a fixed period of time, offering a view of the dynamic development of the system.
"To exploit emergent biomolecules' electric properties for promising applications in energy and environment, it is critical to understand the interfacial behavior of those conducting proteins," he said.
Wei and his team conducted many simulations on Stampede to understand the degree to which decaheme cytochrome sticks to a gold surface in water, and the electron transfer efficiency of the process.
Their results, published in February 2016 in the Journal of Physical Chemistry Letters, showed that dehydration - which involves the loss of a water molecule from the reacting molecule - on the gold surface acts as a vital driving force for protein adsorption.
"If we put those proteins on the electron surface and then we transfer the electron between the outside environment and the inside of the electrode surfaces, we can convert energy or reduce toxic heavy metals through the redox methods," Wei said. "This is very cutting edge, but we see several cool examples already."
Whether through studies of bacterial nano-wires, desalinizing polymers, or protein-ligand binding sensors, exploring the quantum and atomic behavior of molecules has the potential to help researchers understand new and enhanced biomaterials. Wei is also expanding his research to anti-biocorrosion and anti-biofouling materials design.
"These microscopic tools can give you a lot of information," Wei said. "Each type of simulation has limitations, but when we have a strong theoretical background and can connect different scales, we can rationalize experimental structure-function designs and solve important scientific and engineering problems."