TY - JOUR
T1 - Energetic and structural basis for the differences in infectivity between the wild-type and mutant spike proteins of SARS-CoV-2 in the Mexican population
AU - Bello, Martiniano
AU - Hasan, Md Kamrul
AU - Hussain, Nazmul
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/9
Y1 - 2021/9
N2 - SARS-CoV-2 is the causative agent of the ongoing viral pandemic of COVID-19. After the emergence of this virus, it became a global public health concern and quickly evolved into a pandemic. Mexico is currently in the third position in the number of deaths due to SARS-CoV-2. To date, there have been several lineages of SARS-CoV-2 worldwide; in the Mexican population, two variants of the spike protein (S-protein) are found, localized at H49Y and D614G, which have been related to increased infectivity with respect to the wild-type S-protein. To understand how these differences impact the structural behavior of the S-protein of SARS-CoV-2, as well as binding with ACE2, we performed MD simulations combined with the molecular mechanics generalized Born/Poisson-Boltzmann surface area (MMGB(PB)SA) approach starting from X-ray crystallography data. Energetic and structural analysis showed that the differences in infectivity can be explained by differences in affinity of the protein-protein interface between the wild-type and mutant S-protein with ACE2. Conformational analysis showed that molecular recognition between the S-protein and ACE2 is linked to a decrease in the conformational flexibility of wild-type and mutant S-protein; however, an increase in the conformational mobility of ACE2 could also contribute to the binding affinity observed using the MMGB(PB)SA method.
AB - SARS-CoV-2 is the causative agent of the ongoing viral pandemic of COVID-19. After the emergence of this virus, it became a global public health concern and quickly evolved into a pandemic. Mexico is currently in the third position in the number of deaths due to SARS-CoV-2. To date, there have been several lineages of SARS-CoV-2 worldwide; in the Mexican population, two variants of the spike protein (S-protein) are found, localized at H49Y and D614G, which have been related to increased infectivity with respect to the wild-type S-protein. To understand how these differences impact the structural behavior of the S-protein of SARS-CoV-2, as well as binding with ACE2, we performed MD simulations combined with the molecular mechanics generalized Born/Poisson-Boltzmann surface area (MMGB(PB)SA) approach starting from X-ray crystallography data. Energetic and structural analysis showed that the differences in infectivity can be explained by differences in affinity of the protein-protein interface between the wild-type and mutant S-protein with ACE2. Conformational analysis showed that molecular recognition between the S-protein and ACE2 is linked to a decrease in the conformational flexibility of wild-type and mutant S-protein; however, an increase in the conformational mobility of ACE2 could also contribute to the binding affinity observed using the MMGB(PB)SA method.
KW - Binding free energy
KW - COVID-19
KW - Molecular dynamics simulation
KW - SARS-CoV-2
KW - Spike protein
UR - http://www.scopus.com/inward/record.url?scp=85109144517&partnerID=8YFLogxK
U2 - 10.1016/j.jmgm.2021.107970
DO - 10.1016/j.jmgm.2021.107970
M3 - Artículo
C2 - 34242876
AN - SCOPUS:85109144517
SN - 1093-3263
VL - 107
JO - Journal of Molecular Graphics and Modelling
JF - Journal of Molecular Graphics and Modelling
M1 - 107970
ER -