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31 August 2021 | Story Leonie Bolleurs | Photo Supplied
UFS scientists involved in revolutionary protein structure prediction
Left: Dr Ana Ebrecht, a former postdoctoral student of the UFS, was part of the team that validated the data for the Science paper. Right: Prof Dirk Opperman was involved in a revolutionary finding in biology, which predicts the structure of a protein. His work in collaboration with other scientists has been published in Science.

Prof Dirk Opperman, Associate Professor in the Department of Microbiology and Biochemistry at the University of the Free State (UFS), in collaboration with Dr Ana Ebrecht (a former postdoc in the same department) and Prof Albie van Dijk from the Department of Biochemistry at the North-West University (NWU), was part of an international collaboration of researchers who participated in solving an intricate problem in science – accurate protein structure prediction.

The team of researchers recently contributed to an influential paper describing new methods in protein structure prediction using machine learning. The paper was published in the prestigious scientific journal, Science.

“These new prediction methods can be a game changer,” believes Prof Opperman.

“As some proteins simply do not crystalise, this could be the closest we get to a three-dimensional view of the protein. Accurate enough prediction of proteins, each with its own unique three-dimensional shape, can also be used in molecular replacement (MR) instead of laborious techniques such as incorporating heavy metals into the protein structure or replacing sulphur atoms with selenium,” he says.

Having insight into the three-dimensional structure of a protein has the potential to enable more advanced drug discovery, and subsequently, managing diseases.

Exploring several avenues …

According to Prof Opperman, protein structure prediction has been available for many years in the form of traditional homological modelling; however, there was a big possibility of erroneous prediction, especially if no closely related protein structures are known.

Besides limited complementary techniques such as nuclear magnetic resonance (NMR) and electron microscopy (Cryo-EM), he explains that the only way around this is to experimentally determine the structure of the protein through crystallisation and X-ray diffraction. “But it is a quite laborious and long technique,” he says.

Prof Opperman adds that with X-ray diffraction, one also has to deal with what is known in X-ray crystallography as the ‘phase problem’ – solving the protein structure even after you have crystallised the protein and obtained good X-ray diffraction data, as some information is lost.

He states that the phase problem can be overcome if another similar-looking protein has already been determined.

This indeed proved to be a major stumbling block in the determination of bovine glycine N-acyltransferase (GLYAT), a protein crystallised in Prof Opperman’s research group by Dr Ebrecht, currently a postdoc in Prof Van Dijk’s group at the NWU, as no close structural homologous proteins were available.

“The collaboration with Prof Opperman’s research group has allowed us to continue with this research that has been on hold for almost 16 years,” says Prof Van Dijk, who believes the UFS has the resources and facilities for structural research that not many universities in Africa can account for.

The research was conducted under the Synchrotron Techniques for African Research and Technology (START) initiative, funded by the Global Challenges Research Fund (GCRF). After a year and multiple data collections at a specialised facility, Diamond Light Source (synchrotron) in the United Kingdom, the team was still unable to solve the structure.

Dr Carmien Tolmie, a colleague from the UFS Department of Microbiology and Biochemistry, also organised a Collaborative Computational Project Number 4 (CCP4) workshop, attended by several well-known experts in the field. Still, the experts who usually participate in helping students and researchers in structural biology to solve the most complex cases, were stumped by this problem.

Working with artificial intelligence

“We ultimately decided to turn to a technique called sulphur single-wavelength anomalous dispersion (S-SAD), only available at specialised beam-lines at synchrotrons, to solve the phase problem, says Prof Opperman.

Meanwhile, Prof Randy Read from the University of Cambridge, who lectured at the workshop hosted by Dr Tolmie, was aware of the difficulties in solving the GLYAT structure. He also knew of the Baker Lab at the University of Washington, which is working on a new way to predict protein structures; they developed RoseTTAaFold to predict the folding of proteins by only using the amino acid sequence as starting point.

RoseTTAaFold, inspired by AlphaFold 2, the programme of DeepMind (a company that develops general-purpose artificial intelligence (AGI) technology), uses deep learning artificial intelligence (AI) to generate the ‘most-likely’ model. “This turned out to be a win-win situation, as they could accurately enough predict the protein structure for the UFS, and the UFS in turn could validate their predictions,” explains Prof Opperman.

A few days after the predictions from the Baker Lab, the S-SAD experiments at Diamond Light Source confirmed the solution to the problem when they came up with the same answer.

Stunning results in a short time

“Although Baker’s group based their development on the DeepMind programme, the way the software works is not completely the same,” says Dr Ebrecht. “In fact, AlphaFold 2 has a slightly better prediction accuracy. Both, however, came with stunningly good results in an incredibly short time (a few minutes to a few hours),” she says.

Both codes are now freely available, which will accelerate improvements in the field even more. Any researcher can now use that code to develop new software. In addition, RoseTTAFold is offered on a platform accessible to any researcher, even if they lack knowledge in coding and AI.

News Archive

Housing strategy must accommodate special needs
2005-10-17

Dr Mark Napier of the Council for Scientific and Industrial Research (CSIR) 

South Africa’s housing strategy must give attention to people with special needs, including people with disabilities as well as people living with HIV / AIDS and those in poverty.

This was the view expressed by Dr Mark Napier of the Council for Scientific and Industrial Research (CSIR) during his recent presentation to the Housing Research Day organised by the Centre for Development Support (CDS) at the University of the Free State (UFS).

Dr Napier previously worked in the national Department of Housing and was involved in shaping the recently launched “Breaking New Ground” housing strategy of Minister Lindiwe Sisulu. 

He said the changing social and demographic trends in South African society, especially after 11 years of democracy, required more flexibility in housing delivery to address the housing needs of different groups of people.  “For example, there are people who wish to or may be required to be spatially mobile because of their work or other reasons. There are also those communities who are vulnerable to disasters,” he said.

According to Dr Napier, housing delivery faced a number of challenges which needed to be addressed, including:

  • the withdrawal of larger construction firms
  • perceptions of low profit margins in the private sector
  • the slow process of developing an emerging contractor sector
  • access to bridging and other finance
  • the ability to retain capacity and expertise mainly at municipal level
  • the acquisition of well located (especially inner city) land

Dr Napier said the new housing strategy – which is called “Breaking New Ground” – tries to go beyond the provision of basic shelter to the establishment of sustainable settlements. It is also tries to be more responsive to housing demand rather than being supply led.

 The new strategy also allows for greater devolution of power to municipalities in the provision of housing, through accreditation to manage subsidies, Dr Napier said. 

He said a survey of people who had benefited from government’s housing programme had shown mixed results, with beneficiaries reporting a sense of security, independence and pride.  Although the location of the houses was poor and there were increased costs, most beneficiaries said they were better off than before, according to the survey.  Beneficiaries also highlighted the problem that they had very little personal choice between houses, sites or settlements.

There was also the perceived failure of developers and municipalities to repair defective houses or adequately maintain settlements, the survey found.
Many beneficiaries also reported that they felt unsafe in their settlements as well as in their own houses.

Prof Lucius Botes, the director of the Centre for Development Support, said the research day highlighted the Centre’s ability to interact with real problems faced by communities, by government, the private sector and civil society.  “This is how we can ensure that the UFS is engaged through our research with our people’s problems and challenges and enables the UFS as a place of scholarship to assist in finding solutions,” Prof Botes said.

Media release
Issued by:Lacea Loader
Media Representative
Tel:   (051) 401-2584
Cell:  083 645 2454
E-mail:  loaderl.stg@mail.uovs.ac.za
17 October 2005   
 

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