期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：25
页码：13967-13974
DOI：10.1073/pnas.2008209117
出版社：The National Academy of Sciences of the United States of America
摘要：Molecular dynamics and free energy simulations have been carried out to elucidate the structural origin of differential protein–protein interactions between the common receptor protein angiotensin converting enzyme 2 (ACE2) and the receptor binding domains of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [A. E. Gorbalenya et al. , Nat. Microbiol. 5, 536–544 (2020)] that causes coronavirus disease 2019 (COVID-19) [P. Zhou et al. , Nature 579, 270–273 (2020)] and the SARS coronavirus in the 2002–2003 (SARS-CoV) [T. Kuiken et al. , Lancet 362, 263–270 (2003)] outbreak. Analysis of the dynamic trajectories reveals that the binding interface consists of a primarily hydrophobic region and a delicate hydrogen-bonding network in the 2019 novel coronavirus. A key mutation from a hydrophobic residue in the SARS-CoV sequence to Lys417 in SARS-CoV-2 creates a salt bridge across the central hydrophobic contact region, which along with polar residue mutations results in greater electrostatic complementarity than that of the SARS-CoV complex. Furthermore, both electrostatic effects and enhanced hydrophobic packing due to removal of four out of five proline residues in a short 12-residue loop lead to conformation shift toward a more tilted binding groove in the complex in comparison with the SARS-CoV complex. On the other hand, hydrophobic contacts in the complex of the SARS-CoV–neutralizing antibody 80R are disrupted in the SARS-CoV-2 homology complex model, which is attributed to failure of recognition of SARS-CoV-2 by 80R.
关键词：protein–protein interaction ; SARS-CoV-2 ; relative free energy of binding ; molecular dynamics
