A protein researcher at the University of Alabama at Birmingham (UAB) has been found guilty of falsifying data that he used to construct 12 fraudulent protein structures that made it into the scientific literature and an international archive of protein structures.
After investigating the misconduct -- with the help of a committee of independent protein scientists -- the university has asked that the structures be removed from the database and that ten research papers, authored by former UAB researcher H.M. Krishna Murthy over the past decade, be retracted from the literature.
"What we know is that when Dr. Murthy was asked to provide the data behind the structures, there was not sufficient material presented to allow the expert panel to determine the source of the error," Richard Marchase, UAB's vice president for research and economic development, told The Scientist.
The UAB investigation concluded that the structures Murthy proposed violated basic physical and chemical laws, making their existence virtually impossible. "There were just many aspects of the proposed structures that didn't appear to be at all plausible given the physical laws of how proteins come together," added Marchase, who is also UAB's scientific integrity officer.
"I think [Murthy] deserves tarring and feathering," Gert Vriend, a bioinformatician at Radboud University Nijmegen Medical Centre in The Netherlands, told The Scientist.
Murthy, whose UAB contract at the school's Center for Biophysical Sciences and Engineering expired in February of this year with the university opting not to renew it, "has always denied any misconduct," according to Marchase. Murthy could not be reached for comment by email, and UAB is unaware of his current whereabouts.
According to Marchase, the university informed the Office of Research Integrity (ORI) of the U.S. Department of Health & Human Services that UAB was investigating Murthy's suspect structures, and presumably the ORI will now initiate their own investigation of Murthy. But the agency is not talking about the Murthy case yet. "We can neither confirm nor deny that we have such a case," wrote an ORI spokesperson in an email to The Scientist.
Murthy's fraud was uncovered when European crystallographers who were working on some of the same structures that Murthy was claiming to solve raised red flags. Piet Gros, a crystallographer at Utrecht University in The Netherlands, was alerted to potential problems with Murthy's structures by one of his grad students. Gros's lab published a structure for the immune protein C3b in a 2006 issue of Nature. Along with the Gros group's paper, two other papers on the structure of C3b were published in the issue. One was from Murthy's group at UAB and the other from researchers at the biotech company Genentech.
"We noticed quite quickly that there was a problem with the crystal lattice in the Murthy structure," Gros told The Scientist. "There were huge gaps between layers of molecules. That was a huge red flag."
Gros said that he contacted Murthy about the abnormalities, but the UAB researcher brushed aside his concerns. "Basically we were not satisfied with his answers to the questions," Gros said. "He could not give an explanation to us."
Gros and his colleagues began looking into more of Murthy's structures and noticing other "abnormal features." After unsuccessfully trying to get answers from Murthy, they had independent colleagues, including Vriend, analyze the structures and wrote a letter to Nature and to UAB detailing their findings.
Using sophisticated validation software, Gros and his colleagues uncovered several problems with more of Murthy structures. There were unexplained gaps in the packing pattern of amino acids in the structures and contacts between atoms that were unrealistic, and "there was no solvent in the data," according to Gros. "There are things which are physically impossible," he said.
Though the problems with Murthy's data seem glaring, uncovering the fraud required intricate analysis by protein experts. "The structure [of C3b] was strange, but it did require an expert to read from the numbers that something was worrisome," said Vriend.
Murthy was able to publish fraudulent data on 12 protein structure over the span of 10 years in several different journals, such as Nature, Proceedings of the National Academy of Science, Biochemistry, and Cell. At the beginning of this month, the Journal of Biological Chemistry (JBC) retracted one paper that Murthy published in 1999 on the structure of a domain in the dengue virus. According to Marchase, "Another journal is likely to retract but has not yet," but he declined to say which one.
Officials at the Protein Data Bank (PDB), which archives thousands of protein crystal structures from the literature, have removed the structure (dengue virus NS3 serine protease) reported in the JBC paper from its database, and "will make the remaining 11 entries obsolete if and when the corresponding papers are retracted," according to a PDB statement.
Vriend and Gros said that one good thing to come out of the Murthy fraud case is that journals and the protein structure archives are rethinking the process whereby they validate submitted crystal structures. "This appears to be an extremely rare case," Gros said. "But the [validation] process has to be improved. People are discussing processes of doing this better, and I think that will happen, and it's a good thing."
Vriend agreed, adding that the analysis of Murthy's fraud demonstrated the importance of carefully validating proposed crystal structures for proteins. "Protein structures are so important for so many fields in science that they must be right."
Correction (18th December): In the original version of this story, Murthy was said to have been the recipient of five NIH grants this year. The NIH's Research Portfolio Online Reporting Tool, inaccurately lists the UAB email and name of H.M. Krishna Murthy under grants won by Krishna K. Murthy of the Southwest Foundation for Biomedical Research in Texas. Krishna K. Murthy was not involved in any way with the fraud perpetrated by H.M Krishna Murthy, and the subject of this story was not awarded any NIH grants in 2009. The Scientist regrets the error.
After investigating the misconduct -- with the help of a committee of independent protein scientists -- the university has asked that the structures be removed from the database and that ten research papers, authored by former UAB researcher H.M. Krishna Murthy over the past decade, be retracted from the literature.
"What we know is that when Dr. Murthy was asked to provide the data behind the structures, there was not sufficient material presented to allow the expert panel to determine the source of the error," Richard Marchase, UAB's vice president for research and economic development, told The Scientist.
The UAB investigation concluded that the structures Murthy proposed violated basic physical and chemical laws, making their existence virtually impossible. "There were just many aspects of the proposed structures that didn't appear to be at all plausible given the physical laws of how proteins come together," added Marchase, who is also UAB's scientific integrity officer.
"I think [Murthy] deserves tarring and feathering," Gert Vriend, a bioinformatician at Radboud University Nijmegen Medical Centre in The Netherlands, told The Scientist.
Murthy, whose UAB contract at the school's Center for Biophysical Sciences and Engineering expired in February of this year with the university opting not to renew it, "has always denied any misconduct," according to Marchase. Murthy could not be reached for comment by email, and UAB is unaware of his current whereabouts.
According to Marchase, the university informed the Office of Research Integrity (ORI) of the U.S. Department of Health & Human Services that UAB was investigating Murthy's suspect structures, and presumably the ORI will now initiate their own investigation of Murthy. But the agency is not talking about the Murthy case yet. "We can neither confirm nor deny that we have such a case," wrote an ORI spokesperson in an email to The Scientist.
Murthy's fraud was uncovered when European crystallographers who were working on some of the same structures that Murthy was claiming to solve raised red flags. Piet Gros, a crystallographer at Utrecht University in The Netherlands, was alerted to potential problems with Murthy's structures by one of his grad students. Gros's lab published a structure for the immune protein C3b in a 2006 issue of Nature. Along with the Gros group's paper, two other papers on the structure of C3b were published in the issue. One was from Murthy's group at UAB and the other from researchers at the biotech company Genentech.
"We noticed quite quickly that there was a problem with the crystal lattice in the Murthy structure," Gros told The Scientist. "There were huge gaps between layers of molecules. That was a huge red flag."
Gros said that he contacted Murthy about the abnormalities, but the UAB researcher brushed aside his concerns. "Basically we were not satisfied with his answers to the questions," Gros said. "He could not give an explanation to us."
Gros and his colleagues began looking into more of Murthy's structures and noticing other "abnormal features." After unsuccessfully trying to get answers from Murthy, they had independent colleagues, including Vriend, analyze the structures and wrote a letter to Nature and to UAB detailing their findings.
Using sophisticated validation software, Gros and his colleagues uncovered several problems with more of Murthy structures. There were unexplained gaps in the packing pattern of amino acids in the structures and contacts between atoms that were unrealistic, and "there was no solvent in the data," according to Gros. "There are things which are physically impossible," he said.
Though the problems with Murthy's data seem glaring, uncovering the fraud required intricate analysis by protein experts. "The structure [of C3b] was strange, but it did require an expert to read from the numbers that something was worrisome," said Vriend.
Murthy was able to publish fraudulent data on 12 protein structure over the span of 10 years in several different journals, such as Nature, Proceedings of the National Academy of Science, Biochemistry, and Cell. At the beginning of this month, the Journal of Biological Chemistry (JBC) retracted one paper that Murthy published in 1999 on the structure of a domain in the dengue virus. According to Marchase, "Another journal is likely to retract but has not yet," but he declined to say which one.
Officials at the Protein Data Bank (PDB), which archives thousands of protein crystal structures from the literature, have removed the structure (dengue virus NS3 serine protease) reported in the JBC paper from its database, and "will make the remaining 11 entries obsolete if and when the corresponding papers are retracted," according to a PDB statement.
Vriend and Gros said that one good thing to come out of the Murthy fraud case is that journals and the protein structure archives are rethinking the process whereby they validate submitted crystal structures. "This appears to be an extremely rare case," Gros said. "But the [validation] process has to be improved. People are discussing processes of doing this better, and I think that will happen, and it's a good thing."
Vriend agreed, adding that the analysis of Murthy's fraud demonstrated the importance of carefully validating proposed crystal structures for proteins. "Protein structures are so important for so many fields in science that they must be right."
Correction (18th December): In the original version of this story, Murthy was said to have been the recipient of five NIH grants this year. The NIH's Research Portfolio Online Reporting Tool, inaccurately lists the UAB email and name of H.M. Krishna Murthy under grants won by Krishna K. Murthy of the Southwest Foundation for Biomedical Research in Texas. Krishna K. Murthy was not involved in any way with the fraud perpetrated by H.M Krishna Murthy, and the subject of this story was not awarded any NIH grants in 2009. The Scientist regrets the error.
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