RT Journal Article
SR Electronic
T1 Evolution of the SARS-CoV-2 proteome in three dimensions (3D) during the first six months of the COVID-19 pandemic
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.01.406637
DO 10.1101/2020.12.01.406637
A1 Joseph H. Lubin
A1 Christine Zardecki
A1 Elliott M. Dolan
A1 Changpeng Lu
A1 Zhuofan Shen
A1 Shuchismita Dutta
A1 John D. Westbrook
A1 Brian P. Hudson
A1 David S. Goodsell
A1 Jonathan K. Williams
A1 Maria Voigt
A1 Vidur Sarma
A1 Lingjun Xie
A1 Thejasvi Venkatachalam
A1 Steven Arnold
A1 Luz Helena Alfaro Alvarado
A1 Kevin Catalfano
A1 Aaliyah Khan
A1 Erika McCarthy
A1 Sophia Staggers
A1 Brea Tinsley
A1 Alan Trudeau
A1 Jitendra Singh
A1 Lindsey Whitmore
A1 Helen Zheng
A1 Matthew Benedek
A1 Jenna Currier
A1 Mark Dresel
A1 Ashish Duvvuru
A1 Britney Dyszel
A1 Emily Fingar
A1 Elizabeth M. Hennen
A1 Michael Kirsch
A1 Ali A. Khan
A1 Charlotte Labrie-Cleary
A1 Stephanie Laporte
A1 Evan Lenkeit
A1 Kailey Martin
A1 Marilyn Orellana
A1 Melanie Ortiz-Alvarez de la Campa
A1 Isaac Paredes
A1 Baleigh Wheeler
A1 Allison Rupert
A1 Andrew Sam
A1 Katherine See
A1 Santiago Soto Zapata
A1 Paul A. Craig
A1 Bonnie L. Hall
A1 Jennifer Jiang
A1 Julia R. Koeppe
A1 Stephen A. Mills
A1 Michael J. Pikaart
A1 Rebecca Roberts
A1 Yana Bromberg
A1 J. Steen Hoyer
A1 Siobain Duffy
A1 Jay Tischfield
A1 Francesc X. Ruiz
A1 Eddy Arnold
A1 Jean Baum
A1 Jesse Sandberg
A1 Grace Brannigan
A1 Sagar D. Khare
A1 Stephen K. Burley
YR 2020
UL http://biorxiv.org/content/early/2020/12/01/2020.12.01.406637.abstract
AB Three-dimensional structures of SARS-CoV-2 and other coronaviral proteins archived in the Protein Data Bank were used to analyze viral proteome evolution during the first six 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 proteome sequences showed how each one of the 29 viral study proteins have undergone amino acid changes. Structural models computed for every unique sequence variant revealed that most substitutions map to protein surfaces and boundary layers with a minority affecting hydrophobic cores. Conservative changes were observed more frequently in cores versus boundary layers/surfaces. Active sites and protein-protein interfaces showed modest numbers of substitutions. 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 six drug discovery targets and four structural proteins comprising the virion, highlighting substitutions with the potential to impact protein structure, enzyme activity, and functional 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.Competing Interest StatementThe authors have declared no competing interest.