Evolution of the SARS-CoV-2 proteome in three dimensions (3D) during the first 6 months of the COVID-19 pandemic
Joseph H. Lubin
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorChristine Zardecki
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Research Collaboratory for Structural Bioinformatics Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorElliott M. Dolan
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorChangpeng Lu
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorZhuofan Shen
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorShuchismita Dutta
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Research Collaboratory for Structural Bioinformatics Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
Search for more papers by this authorJohn D. Westbrook
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Research Collaboratory for Structural Bioinformatics Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
Search for more papers by this authorBrian P. Hudson
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Research Collaboratory for Structural Bioinformatics Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorDavid S. Goodsell
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Research Collaboratory for Structural Bioinformatics Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
The Scripps Research Institute, La Jolla, California, USA
Search for more papers by this authorJonathan K. Williams
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorMaria Voigt
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Research Collaboratory for Structural Bioinformatics Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorVidur Sarma
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorLingjun Xie
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorThejasvi Venkatachalam
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorSteven Arnold
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorLuz Helena Alfaro Alvarado
Grinnell College, Grinnell, Iowa, USA
Search for more papers by this authorKevin Catalfano
University of Notre Dame, Notre Dame, Indiana, USA
Search for more papers by this authorAaliyah Khan
University of Maryland Baltimore County, Baltimore, Maryland, USA
Search for more papers by this authorErika McCarthy
Stevens Institute of Technology, Hoboken, New Jersey, USA
Search for more papers by this authorSophia Staggers
Frostburg State University, Frostburg, Maryland, USA
Search for more papers by this authorBrea Tinsley
Youngstown State University, Youngstown, Ohio, USA
Search for more papers by this authorAlan Trudeau
University of Central Florida, Orlando, Florida, USA
Search for more papers by this authorJitendra Singh
New York City College of Technology, Brooklyn, New York, USA
Search for more papers by this authorLindsey Whitmore
Howard University, Washington, District of Columbia, USA
Search for more papers by this authorHelen Zheng
Watchung Hills Regional High School, Warren, New Jersey, USA
Search for more papers by this authorMark Dresel
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorBritney Dyszel
Ursinus College, Collegeville, Pennsylvania, USA
Search for more papers by this authorElizabeth M. Hennen
Roger Williams University, Bristol, Rhode Island, USA
Search for more papers by this authorStephanie Laporte
Brandeis University, Waltham, Massachusetts, USA
Search for more papers by this authorEvan Lenkeit
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorMelanie Ortiz-Alvarez de la Campa
University of Puerto Rico-Rio Piedras, San Juan, Puerto Rico
Search for more papers by this authorAndrew Sam
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorKatherine See
Rochester Institute of Technology, Rochester, New York, USA
Search for more papers by this authorPaul A. Craig
Rochester Institute of Technology, Rochester, New York, USA
Search for more papers by this authorJennifer Jiang
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorRebecca Roberts
Ursinus College, Collegeville, Pennsylvania, USA
Search for more papers by this authorYana Bromberg
Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
Search for more papers by this authorJ. Steen Hoyer
Department of Ecology, Evolution and Natural Resources, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
Search for more papers by this authorSiobain Duffy
Department of Ecology, Evolution and Natural Resources, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
Search for more papers by this authorJay Tischfield
Department of Genetics, Rutgers, The State University of New Jersey, and Human Genetics Institute of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorFrancesc X. Ruiz
Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorEddy Arnold
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorJean Baum
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorJesse Sandberg
Center for Computational and Integrative Biology, Rutgers, The State University of New Jersey, Camden, New Jersey, USA
Search for more papers by this authorGrace Brannigan
Center for Computational and Integrative Biology, Rutgers, The State University of New Jersey, Camden, New Jersey, USA
Department of Physics, Rutgers, The State University of New Jersey, Camden, New Jersey, USA
Search for more papers by this authorCorresponding Author
Sagar D. Khare
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
Correspondence
Sagar D. Khare, Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Email: [email protected]
Stephen K. Burley, Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Stephen K. Burley
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Research Collaboratory for Structural Bioinformatics Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
Research Collaboratory for Structural Bioinformatics Protein Data Bank, San Diego Supercomputer Center, University of California, San Diego, La Jolla, California, USA
Correspondence
Sagar D. Khare, Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Email: [email protected]
Stephen K. Burley, Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Email: [email protected]
Search for more papers by this authorJoseph H. Lubin
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorChristine Zardecki
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Research Collaboratory for Structural Bioinformatics Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorElliott M. Dolan
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorChangpeng Lu
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorZhuofan Shen
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorShuchismita Dutta
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Research Collaboratory for Structural Bioinformatics Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
Search for more papers by this authorJohn D. Westbrook
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Research Collaboratory for Structural Bioinformatics Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
Search for more papers by this authorBrian P. Hudson
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Research Collaboratory for Structural Bioinformatics Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorDavid S. Goodsell
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Research Collaboratory for Structural Bioinformatics Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
The Scripps Research Institute, La Jolla, California, USA
Search for more papers by this authorJonathan K. Williams
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorMaria Voigt
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Research Collaboratory for Structural Bioinformatics Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorVidur Sarma
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorLingjun Xie
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorThejasvi Venkatachalam
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorSteven Arnold
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorLuz Helena Alfaro Alvarado
Grinnell College, Grinnell, Iowa, USA
Search for more papers by this authorKevin Catalfano
University of Notre Dame, Notre Dame, Indiana, USA
Search for more papers by this authorAaliyah Khan
University of Maryland Baltimore County, Baltimore, Maryland, USA
Search for more papers by this authorErika McCarthy
Stevens Institute of Technology, Hoboken, New Jersey, USA
Search for more papers by this authorSophia Staggers
Frostburg State University, Frostburg, Maryland, USA
Search for more papers by this authorBrea Tinsley
Youngstown State University, Youngstown, Ohio, USA
Search for more papers by this authorAlan Trudeau
University of Central Florida, Orlando, Florida, USA
Search for more papers by this authorJitendra Singh
New York City College of Technology, Brooklyn, New York, USA
Search for more papers by this authorLindsey Whitmore
Howard University, Washington, District of Columbia, USA
Search for more papers by this authorHelen Zheng
Watchung Hills Regional High School, Warren, New Jersey, USA
Search for more papers by this authorMark Dresel
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorBritney Dyszel
Ursinus College, Collegeville, Pennsylvania, USA
Search for more papers by this authorElizabeth M. Hennen
Roger Williams University, Bristol, Rhode Island, USA
Search for more papers by this authorStephanie Laporte
Brandeis University, Waltham, Massachusetts, USA
Search for more papers by this authorEvan Lenkeit
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorMelanie Ortiz-Alvarez de la Campa
University of Puerto Rico-Rio Piedras, San Juan, Puerto Rico
Search for more papers by this authorAndrew Sam
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorKatherine See
Rochester Institute of Technology, Rochester, New York, USA
Search for more papers by this authorPaul A. Craig
Rochester Institute of Technology, Rochester, New York, USA
Search for more papers by this authorJennifer Jiang
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorRebecca Roberts
Ursinus College, Collegeville, Pennsylvania, USA
Search for more papers by this authorYana Bromberg
Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
Search for more papers by this authorJ. Steen Hoyer
Department of Ecology, Evolution and Natural Resources, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
Search for more papers by this authorSiobain Duffy
Department of Ecology, Evolution and Natural Resources, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
Search for more papers by this authorJay Tischfield
Department of Genetics, Rutgers, The State University of New Jersey, and Human Genetics Institute of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorFrancesc X. Ruiz
Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorEddy Arnold
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorJean Baum
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Search for more papers by this authorJesse Sandberg
Center for Computational and Integrative Biology, Rutgers, The State University of New Jersey, Camden, New Jersey, USA
Search for more papers by this authorGrace Brannigan
Center for Computational and Integrative Biology, Rutgers, The State University of New Jersey, Camden, New Jersey, USA
Department of Physics, Rutgers, The State University of New Jersey, Camden, New Jersey, USA
Search for more papers by this authorCorresponding Author
Sagar D. Khare
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
Correspondence
Sagar D. Khare, Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Email: [email protected]
Stephen K. Burley, Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Stephen K. Burley
Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Research Collaboratory for Structural Bioinformatics Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
Research Collaboratory for Structural Bioinformatics Protein Data Bank, San Diego Supercomputer Center, University of California, San Diego, La Jolla, California, USA
Correspondence
Sagar D. Khare, Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Email: [email protected]
Stephen K. Burley, Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Email: [email protected]
Search for more papers by this authorFunding information: Division of Biological Infrastructure, Grant/Award Number: DBI-1832184; Division of Chemical, Bioengineering, Environmental, and Transport Systems, Grant/Award Number: CBET1923691; National Cancer Institute, Grant/Award Number: R01 GM133198; National Institute of Allergy and Infectious Diseases; National Institute of General Medical Sciences, Grant/Award Numbers: GM008339, GM135141, R01 GM132565; National Institutes of Health, Grant/Award Numbers: GM136431, R0137 AI027690; National Science Foundation, Grant/Award Numbers: IUSE 1709170, IUSE 1709278, IUSE 1709355, IUSE 1709805; U.S. Department of Energy, Grant/Award Number: DE-SC0019749; New Jersey Space Grant Consortium; Busch Biomedical Foundation
Abstract
Understanding the molecular evolution of the SARS-CoV-2 virus as it continues to spread in communities around the globe is important for mitigation and future pandemic preparedness. Three-dimensional structures of SARS-CoV-2 proteins and those of other coronavirusess archived in the Protein Data Bank were used to analyze viral proteome evolution during the first 6 months of the COVID-19 pandemic. Analyses of spatial locations, chemical properties, and structural and energetic impacts of the observed amino acid changes in >48 000 viral isolates revealed how each one of 29 viral proteins have undergone amino acid changes. Catalytic residues in active sites and binding residues in protein–protein interfaces showed modest, but significant, numbers of substitutions, highlighting the mutational robustness of the viral proteome. Energetics calculations showed that the impact of substitutions on the thermodynamic stability of the proteome follows a universal bi-Gaussian distribution. Detailed results are presented for potential drug discovery targets and the four structural proteins that comprise the virion, highlighting substitutions with the potential to impact protein structure, enzyme activity, and protein–protein and protein–nucleic acid interfaces. Characterizing the evolution of the virus in three dimensions provides testable insights into viral protein function and should aid in structure-based drug discovery efforts as well as the prospective identification of amino acid substitutions with potential for drug resistance.
CONFLICT OF INTEREST
The authors declare no competing financial interests.
Open Research
DATA AVAILABILITY STATEMENT
The computed 3D structural models and energetics results are made freely available under Creative Commons license CC0 for researchers wishing to perform further computational and experimental studies (see https://iqb.rutgers.edu/covid-19_proteome_evolution and https://doi.org/10.5281/zenodo.5521766).
Supporting Information
| Filename | Description |
|---|---|
| prot26250-sup-0001-supinfo.docxWord 2007 document , 5.3 MB | Appendix S1: Supporting information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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