Though it is a cornerstone of virtually every process that occurs in living organisms, the proper folding and transport of biological proteins is a notoriously difficult and time-consuming process to experimentally study.
In a new paper published in eLife, researchers in the School of Biological Sciences and the School of Computer Science have shown that AF2Complex may be able to lend a hand.
Building on the models of DeepMind’s AlphaFold 2, a machine learning tool able to predict the detailed three-dimensional structures of individual proteins, AF2Complex — short for AlphaFold 2 Complex — is a deep learning tool designed to predict the physical interactions of multiple proteins. With these predictions, AF2Complex is able to calculate which proteins are likely to interact with each other to form functional complexes in unprecedented detail.
“We essentially conduct computational experiments that try to figure out the atomic details of supercomplexes (large interacting groups of proteins) important to biological functions,” explained Jeffrey Skolnick, Regents’ Professor and Mary and Maisie Gibson Chair in the School of Biological Sciences, and one of the corresponding authors of the study. With AF2Complex, which was developed last year by the same research team, it’s “like using a computational microscope powered by deep learning and supercomputing.”
In their latest study, the researchers used this ‘computational microscope’ to examine a complicated protein synthesis and transport pathway, hoping to clarify how proteins in the pathway interact to ultimately transport a newly synthesized protein from the interior to the outer membrane of the bacteria — and identify players that experiments might have missed. Insights into this pathway may identify new targets for antibiotic and therapeutic design while providing a foundation for using AF2Complex to computationally expedite this type of biology research as a whole.
Computing complexes
Created by London-based artificial intelligence lab DeepMind, AlphaFold 2 is a deep learning tool able to generate accurate predictions about the three-dimensional structure of single proteins using just their building blocks, amino acids. Taking things a step further, AF2Complex uses these structures to predict the likelihood that proteins are able to interact to form a functional complex, what aspects of each structure are the likely interaction sites, and even what protein complexes are likely to pair up to create even larger functional groups called supercomplexes.
“The successful development of AF2Complex earlier this year makes us believe that this approach has tremendous potential in identifying and characterizing the set of protein-protein interactions important to life,” shared Mu Gao, a senior research scientist at Georgia Tech. “To further convince the broad molecular biology community, we [had to] demonstrate it with a more convincing, high impact application.”
The researchers chose to apply AF2Complex to a pathway in Escherichia coli (E. coli), a model organism in life sciences research commonly used for experimental DNA manipulation and protein production due to its relative simplicity and fast growth.
To demonstrate the tool’s power, the team examined the synthesis and transport of proteins that are essential for exchanging nutrients and responding to environmental stressors: outer membrane proteins, or OMPs for short. These proteins reside on the outermost membrane of gram-negative bacteria, a large family of bacteria characterized by the presence of inner and outer membranes, like E. coli. However, the proteins are created inside the cell and must be transported to their final destinations.
“After more than two decades of experimental studies, researchers have identified some of the protein complexes of key players, but certainly not all of them,” Gao explained. AF2Complex “could enable us to discover some novel and interesting features of the OMP biogenesis pathway that were missed in previous experimental studies.”
New insights
Using the Summit supercomputer at the Oak Ridge National Laboratory, the team, which included computer science undergraduate Davi Nakajima An, put AF2Complex to the test. They compared a few proteins known to be important in the synthesis and transport of OMPs to roughly 1,500 other proteins — all of the known proteins in E. coli’s cell envelope — to see which pairs the tool computed as most likely to interact, and which of those pairs were likely to form supercomplexes.
To determine if AF2Complex’s predictions were correct, the researchers compared the tool’s predictions to known experimental data. “Encouragingly,” said Skolnick, “among the top hits from computational screening, we found previously known interacting partners.” Even within those protein pairs known to interact, AF2Complex was able to highlight structural details of those interactions that explain data from previous experiments, lending additional confidence to the tool’s accuracy.
In addition to known interactions, AF2Complex predicted several unknown pairs. Digging further into these unexpected partners revealed details on what aspects of the pairs might interact to form larger groups of functional proteins, likely active configurations of complexes that have previously eluded experimentalists, and new potential mechanisms for how OMPs are synthesized and transported.
“Since the outer membrane pathway is both vital and unique to gram-negative bacteria, the key proteins involved in this pathway could be novel targets for new antibiotics,” said Skolnick. “As such, our work that provides molecular insights about these new drug targets might be valuable to new therapeutic design.”
Beyond this pathway, the researchers are hopeful that AF2Complex could mean big things for biology research.
“Unlike predicting structures of a single protein sequence, predicting the structural model of a supercomplex can be very complicated, especially when the components or stoichiometry of the complex is unknown,” Gao noted. “In this regard, AF2Complex could be a new computational tool for biologists to conduct trial experiments of different combinations of proteins,” potentially expediting and increasing the efficiency of this type of biology research as a whole.
AF2Complex is an open-source tool available to the public and can be downloaded here.
This work was supported in part by the DOE Office of Science, Office of Biological and Environmental Research (DOE DE-SC0021303) and the Division of General Medical Sciences of the National Institute Health (NIH R35GM118039). DOI: https://doi.org/10.7554
Meike Van der Heijden, PhD
Postdoctoral Associate
Sillitoe Lab
Department of Pathology
Baylor College of Medicine
Livestream via Zoom
SPEAKER BIO
The cerebellum’s protracted developmental timeline makes its maturational program remarkably sensitive to genetic, mechanical, and environmental perturbations. Early cerebellar perturbations can cause diverse neurodevelopmental disabilities in infants, including motor, cognitive, affective, and social deficits. The postnatal cerebellar development of mice uniquely situates this model for in vivo investigation of the dynamics that orchestrate functional circuit maturation. My research goal is to define how the developing cerebellum becomes a functional circuit and to understand why early cerebellar perturbations cause diverse neurodevelopmental deficits. My previous work showed that neural signal maturation relies on the interaction between diverse developmental lineages, that cerebellar-dependent motor and non-motor behaviors differentially rely on distinct neural pathways, and that unique cerebellar neural signal signatures predict various motor impairments. In my lab, we will build on these findings by identifying how neural signals mature, how diverse cerebellar functions are anatomically segregated, and how disease-associated neural signals are propagated in the cerebellar circuit. By bridging developmental and systems neuroscience, this understanding will allow us to appreciate how developmental perturbations can cause diverse neurodevelopmental deficits. Next, we can use this basic knowledge to generate therapies that mimic natural developmental processes. Ultimately, we will employ this understanding to predict, prevent, and reverse neurodevelopmental deficits.
Hosted by: Dr. Patrick McGrath
Event Details
The Institute for Advanced Study (IAS) recently awarded Georgia Tech Bioinformatics Graduate Program Ph.D. student Breanna Shi the Advanced Graduate Ambassadorship from their Women and Mathematics program. As part of this award, Shi will organize a workshop to address equity by using her math background to help other underrepresented graduate students across Georgia Tech’s College of Sciences learn and apply math and computational methods in their research.
Associate Professor of Biological Sciences and Biological Sciences Graduate Committee Chair Ingeborg Schmidt-Krey first met Shi during her recruitment into the Bioinformatics (BINF) Ph.D. program, which is directed by Professor King Jordan, and is one of five Ph.D. programs and two M.S. programs in the School of Biological Sciences at Tech. Shi impressed Schmidt-Krey during her second semester as an engaged student — particularly in research ethics discussions.
“Bree’s background in mathematics coupled with her passion for applying mathematical approaches to biological research made her a fantastic match for such an interdisciplinary program,” said Schmidt-Krey. “Bree has a particular interest in using machine learning in her research and making her skills accessible to other students via her symposium, outreach activities, and teaching.”
Shi first contacted Biological Sciences Associate Professor Patrick McGrath about coming to Georgia Tech to join the Bioinformatics program. “With her mathematical background and interest in genomics, I thought that she would be a great match for this program and Georgia Tech in general,” McGrath said.
“Now in her second year, Breanna is fully participating in our lab’s research,” he added. “She’s using her skills in machine learning and computational biology to understand the evolution of behavior in Lake Malawi cichlids, a large flock of species that have evolved a variety of new social behaviors.”
Schmidt-Krey shared that Shi advocates for graduate students via the Georgia Tech Student Government Association (SGA), is working towards the Tech to Teaching certificate in preparation for her plans to become a professor, participates in several underrepresented minority recruitment activities, and is an instructor in the VIP program, where she will involve undergraduates from various backgrounds in her research.
“Bree is currently supported by a GEM Fellowship and GAANN award. Bree's symposium impressively shows a second-year Ph.D. student's initiative and commitment to equity in our community.”
Shi has also been awarded the Graduate Fellowship for STEM Diversity (GFSD) and the Graduate Retaining Inspirational Scholars in Technology and Engineering (Grad RISE) from Georgia Tech’s Center for Engineering Education and Diversity (CEED).
“Bree’s research includes looking for particular neurons in the brain that are activated during reproductive behaviors,” said McGrath, who is now Shi’s advisor.
McGrath added that Shi is also passionate about using new technologies to study aggression behaviors, simulating virtual fish to induce and learn from aggressive behaviors in other fish.
Currently overseeing a large group of undergraduate and master’s students, Shi is also passionate about mentorship, adding that she became interested in education research through her time with the Georgia Tech Center for Teaching and Learning.
“While I was initially nervous about having her overseeing so many students so early in her career, Breanna has really done an outstanding job of overseeing this group,” McGrath shared. “Her goal is to become an academic professor, so it's great to see her display these skills. I am very proud of what Breanna has accomplished in such a short time.”
Shi’s mentorship will continue with the IAS workshop. “[The workshop] will be a partnership with Christin Salley, a third year Ph.D. student in Civil Engineering who is also a GEM fellow,” Shi said.
“Our hope is to get graduate students interested in using mathematics and computer science into their research,” Shi said. “As diversity fellows, Christin and I are making it a priority to include students from diverse groups and to facilitate mentoring.”
They also hope to provide a collaborative environment where students can network and learn. “Our goal is to host this event annually,” Shi added.
Shi, who has two degrees in mathematics, has been interested to understand why some students find math and computer sciences (CS) difficult to master. She hopes to employ a few non-traditional techniques that will allow students to feel less resistant and more understanding of the subjects. “We hope to provide greater outcomes for the participants than their past experiences with math and CS.”
The Institute for Advanced Study (IAS) recently awarded Georgia Tech Bioinformatics Graduate Program Ph.D. student Breanna Shi the Advanced Graduate Ambassadorship from their Women and Mathematics program. As part of this award, Shi will organize a workshop to address equity by using her math background to help other underrepresented graduate students across Georgia Tech’s College of Sciences learn and apply math and computational methods in their research.
Associate Professor of Biological Sciences and Biological Sciences Graduate Committee Chair Ingeborg Schmidt-Krey first met Shi during her recruitment into the Bioinformatics (BINF) Ph.D. program, which is directed by Professor King Jordan, and is one of five Ph.D. programs and two M.S. programs in the School of Biological Sciences at Tech. Shi impressed Schmidt-Krey during her second semester as an engaged student — particularly in research ethics discussions.
“Bree’s background in mathematics coupled with her passion for applying mathematical approaches to biological research made her a fantastic match for such an interdisciplinary program,” said Schmidt-Krey. “Bree has a particular interest in using machine learning in her research and making her skills accessible to other students via her symposium, outreach activities, and teaching.”
Shi first contacted Biological Sciences Associate Professor Patrick McGrath about coming to Georgia Tech to join the Bioinformatics program. “With her mathematical background and interest in genomics, I thought that she would be a great match for this program and Georgia Tech in general,” McGrath said.
“Now in her second year, Breanna is fully participating in our lab’s research,” he added. “She’s using her skills in machine learning and computational biology to understand the evolution of behavior in Lake Malawi cichlids, a large flock of species that have evolved a variety of new social behaviors.”
Schmidt-Krey shared that Shi advocates for graduate students via the Georgia Tech Student Government Association (SGA), is working towards the Tech to Teaching certificate in preparation for her plans to become a professor, participates in several underrepresented minority recruitment activities, and is an instructor in the VIP program, where she will involve undergraduates from various backgrounds in her research.
“Bree is currently supported by a GEM Fellowship and GAANN award. Bree's symposium impressively shows a second-year Ph.D. student's initiative and commitment to equity in our community.”
Shi has also been awarded the Graduate Fellowship for STEM Diversity (GFSD) and the Graduate Retaining Inspirational Scholars in Technology and Engineering (Grad RISE) from Georgia Tech’s Center for Engineering Education and Diversity (CEED).
“Bree’s research includes looking for particular neurons in the brain that are activated during reproductive behaviors,” said McGrath, who is now Shi’s advisor.
McGrath added that Shi is also passionate about using new technologies to study aggression behaviors, simulating virtual fish to induce and learn from aggressive behaviors in other fish.
Currently overseeing a large group of undergraduate and master’s students, Shi is also passionate about mentorship, adding that she became interested in education research through her time with the Georgia Tech Center for Teaching and Learning.
“While I was initially nervous about having her overseeing so many students so early in her career, Breanna has really done an outstanding job of overseeing this group,” McGrath shared. “Her goal is to become an academic professor, so it's great to see her display these skills. I am very proud of what Breanna has accomplished in such a short time.”
Shi’s mentorship will continue with the IAS workshop. “[The workshop] will be a partnership with Christin Salley, a third year Ph.D. student in Civil Engineering who is also a GEM fellow,” Shi said.
“Our hope is to get graduate students interested in using mathematics and computer science into their research,” Shi said. “As diversity fellows, Christin and I are making it a priority to include students from diverse groups and to facilitate mentoring.”
They also hope to provide a collaborative environment where students can network and learn. “Our goal is to host this event annually,” Shi added.
Shi, who has two degrees in mathematics, has been interested to understand why some students find math and computer sciences (CS) difficult to master. She hopes to employ a few non-traditional techniques that will allow students to feel less resistant and more understanding of the subjects. “We hope to provide greater outcomes for the participants than their past experiences with math and CS.”
The Georgia Institute of Technology will hold its Fall 2022 Commencement ceremonies Dec. 16 – 17 at Bobby Dodd Stadium.
This semester's ceremonies celebrate 1,690 summer graduates and 3,930 fall graduates — 1,500 bachelor’s students, 3,760 master’s students, and 360 doctoral students across both semesters.
As part of the ceremonies, three distinguished speakers will address graduates as they embark on their post-graduate lives and careers. All three are familiar with the Georgia Tech experience, either as a student or faculty member — and one is a College of Sciences alumna.
The Georgia Institute of Technology will hold its Fall 2022 Commencement ceremonies Dec. 16 – 17 at Bobby Dodd Stadium.
This semester's ceremonies celebrate 1,690 summer graduates and 3,930 fall graduates — 1,500 bachelor’s students, 3,760 master’s students, and 360 doctoral students across both semesters.
As part of the ceremonies, three distinguished speakers will address graduates as they embark on their post-graduate lives and careers. All three are familiar with the Georgia Tech experience, either as a student or faculty member — and one is a College of Sciences alumna.
Nine new Faculty Fellows were appointed to the Brook Byers Institute for Sustainable Systems (BBISS). In addition to their own work, BBISS Fellows serve as a board of advisors to the BBISS; foster the culture and community of sustainability researchers, educators, and students at Georgia Tech; and communicate broadly the vision, mission, values, and objectives of the BBISS. Fellows will work with the BBISS for three years, with the potential for a renewed term.
The BBISS Faculty Fellows program has been in place since 2014. Fellows will number between 10 and 15, will be drawn from across all 6 colleges and GTRI at Georgia Tech. It is expected that annual allowances provided to each BBISS Fellow will range from $1000 to $1500 depending on number of fellows in the program and availability of funds.
The new BBISS Faculty Fellows are:
- Joe Bozeman – Assistant Professor, School of Civil and Environmental Engineering
- Dylan Brewer - Assistant Professor, School of Economics
- Andre Calmon – Assistant Professor, Scheller College of Business
- Brian Gunter - Associate Professor, Daniel Guggenheim School of Aerospace Engineering
- Jenny McGuire – Assistant Professor, School of Earth and Atmospheric Sciences and School of Biological Sciences
- Jessica Roberts – Assistant Professor, College of Computing
- Ilan Stern – Senior Research Scientist, Georgia Tech Research Institute
- Anjali Thomas - Associate Professor, Sam Nunn School of International Affairs
- Zhaohui Tong - Associate Professor, School of Chemical & Biomolecular Engineering
These faculty members join the current roster of Faculty Fellows:
- Baabak Ashuri - Associate Professor, School of Building Construction
- Kevin Caravati – Principal Research Scientist, Georgia Tech Research Institute
- Ellen Dunham-Jones – Professor, School of Architecture
- Daniel Matisoff - Associate Professor, School of Public Policy
- Kate Pride Brown - Associate Professor, School of History and Sociology
- Perry Yang – Professor, School of City and Regional Planning
More information can be found on the BBISS website.
Nine new Faculty Fellows were appointed to the Brook Byers Institute for Sustainable Systems (BBISS). In addition to their own work, BBISS Fellows serve as a board of advisors to the BBISS; foster the culture and community of sustainability researchers, educators, and students at Georgia Tech; and communicate broadly the vision, mission, values, and objectives of the BBISS. Fellows will work with the BBISS for three years, with the potential for a renewed term.
The BBISS Faculty Fellows program has been in place since 2014. Fellows will number between 10 and 15, will be drawn from across all 6 colleges and GTRI at Georgia Tech. It is expected that annual allowances provided to each BBISS Fellow will range from $1000 to $1500 depending on number of fellows in the program and availability of funds.
The new BBISS Faculty Fellows are:
- Joe Bozeman – Assistant Professor, School of Civil and Environmental Engineering
- Dylan Brewer - Assistant Professor, School of Economics
- Andre Calmon – Assistant Professor, Scheller College of Business
- Brian Gunter - Associate Professor, Daniel Guggenheim School of Aerospace Engineering
- Jenny McGuire – Assistant Professor, School of Earth and Atmospheric Sciences and School of Biological Sciences
- Jessica Roberts – Assistant Professor, College of Computing
- Ilan Stern – Senior Research Scientist, Georgia Tech Research Institute
- Anjali Thomas - Associate Professor, Sam Nunn School of International Affairs
- Zhaohui Tong - Associate Professor, School of Chemical & Biomolecular Engineering
These faculty members join the current roster of Faculty Fellows:
- Baabak Ashuri - Associate Professor, School of Building Construction
- Kevin Caravati – Principal Research Scientist, Georgia Tech Research Institute
- Ellen Dunham-Jones – Professor, School of Architecture
- Daniel Matisoff - Associate Professor, School of Public Policy
- Kate Pride Brown - Associate Professor, School of History and Sociology
- Perry Yang – Professor, School of City and Regional Planning
More information can be found on the BBISS website.
For marine scientist, climate activist, and Tech alumnus Albert George (MS HSTS 2009), the fight against climate change is also a fight for home.
Now, what started as a citizen science initiative led by George has turned into a $2.6 million National Fish and Wildlife Association effort to restore degraded salt marshes in Charleston, South Carolina. As part of the project, Joel Kostka, professor and associate chair of Research in the School of Biological Sciences, will lead a team of researchers to not only monitor these restoration efforts, but gain insights into why the marshes degraded in the first place — and how to prevent it from happening in the future.
Over the past three years, Kostka, who has a joint appointment in the School of Earth and Atmospheric Sciences, has worked with SCDNR and Robinson Design Engineers, a local firm co-led by Tech alum Joshua Robinson (CEE 2005), to develop engineering and design plans for the restoration of the salt marshes.
“That project went really well,” shared Kostka, “and now we have developed engineering and design plans for the actual restoration as we are moving forward with the next phase.”
Work for the current phase of the project is set to begin soon. Over the next four years, community volunteers will work to plant marsh grasses, restore oyster reefs, and excavate the tidal creeks that supply the marsh with sea water.
“Because if we don't do this work,” George shared, “then basically it means a place that I grew up in and a place that I call home will no longer exist.”
Georgia Tech Community-Wide Campaign Event on December 10th
Please join us for a campaign launch event for students, alumni, faculty, and staff.
Enjoy free food and giveaways, along with interactive experiences with students and alumni as they describe their startups developed through CREATE-X and showcase their work in robotics and artificial intelligence. Test your Tech knowledge on the Tech Trivia Wall and listen to engaging speakers.
Event Details
December 10, 2022
11 a.m. to 2 p.m.
Speaker Program begins at 12 p.m.
Speaker lineup:
- Jenny Moore, AE 2005, “From Freshman Calc to 5th Gen Fighters”
- Jimmy Mitchell, CE 2005, “Building Sustainability Through Progress & Service”
- Tom Fanning, IMGT 1979, M.S. IMGT 1980, HON Ph.D. 2013, “Three Spheres: Southern Company chairman, president & CEO Tom Fanning shares how energy security breeds economic security, which in turn breeds national security”
- Jean Marie Richardson, MGT 2002, “Set Your Intentions to Build the Future”
Jenny “Juno” Moore, AE 2005, is an F-35 Training and Operations subject matter expert, flight instructor, and fighter pilot.
Jimmy Mitchell, CE 2005, is senior director of business development at Skanska and one of Georgia’s first LEED managers, the creator of the Atlanta Mission urban garden, and a founding board member of the Lifecycle Building Center, the construction material reuse nonprofit based in Atlanta. His project experience includes the Kendeda Building for Innovative Sustainable Design, a fully certified Living Building Challenge project.
Tom Fanning, IMGT 1979, M.S. IMGT 1980, HON Ph.D. 2013, is the chairman, president & CEO of Southern Company.
Jean Marie Richardson, MGT 2002, is the founder and CEO of iFOLIO, an Atlanta-based, rapidly growing tech company.
Transform tomorrow, together. Visit transformingtomorrow.gatech.edu for more information.
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