pubs.acs.

org/JPCL Letter

Immune Escape Mechanisms of SARS-CoV‑2 Delta and Omicron

Variants against Two Monoclonal Antibodies That Received
Emergency Use Authorization
Danyang Xiong, Xiaoyu Zhao, Song Luo, Yalong Cong, John Z. H. Zhang,* and Lili Duan*
Cite This: J. Phys. Chem. Lett. 2022, 13, 6064−6073 Read Online

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ABSTRACT: Multiple-site mutated SARS-CoV-2 Delta and Omicron variants may trigger
immune escape against existing monoclonal antibodies. Here, molecular dynamics
simulations combined with the interaction entropy method reveal the escape mechanism
of Delta/Omicron variants to Bamlanivimab/Etesevimab. The result shows the
significantly reduced binding affinity of the Omicron variant for both antibodies, due to
the introduction of positively charged residues that greatly weaken their electrostatic
interactions. Meanwhile, significant structural deflection induces fewer atomic contacts and
an unstable binding mode. As for the Delta variant, the reduced binding affinity for
Bamlanivimab is owing to the alienation of the receptor-binding domain to the main part
of this antibody, and the binding mode of the Delta variant to Etesevimab is similar to that
of the wild type, suggesting that Etesevimab could still be effective against the Delta
variant. We hope this work will provide timely theoretical insights into developing
antibodies to prevalent and possible future variants of SARS-CoV-2.

C oronavirus disease 2019 (COVID-19), caused by the

severe acute respiratory syndrome coronavirus 2 (SARS-
CoV-2), is spreading globally, with more than 520 million
confirmed cases and 6 million deaths as of June 2022.1 As a
member of the coronavirus family, SARS-CoV-2 belongs to the
β genus single-stranded RNA viruses, and its surface
transmembrane spike glycoprotein (S-protein) can specifically
recognize the host cell receptor angiotensin-converting enzyme
2 (ACE2) through the receptor-binding domain (RBD) to
mediate virus invasion.2−4 This process has been identified as a
critical step of viral infection in the body, and the RBD has also
become a significant target for drug and antibody research.5,6
Currently, monoclonal antibodies (mAbs) are promising for
treating and preventing COVID-19, and the effectiveness of
various mAbs has been validated. 7−11 Among them,
Bamlanivimab (LY-CoV555) and Etesevimab (LY-CoV016)
have received emergency use authorization (EUA) from the
U.S. Food and Drug Administration (FDA) for the treatment
of patients with mild to moderate symptoms due to their good
response in clinical trials.12,13 They are both RBD-targeting
antibodies and can specifically bind to the RBD and interfere
with the regular recognition between the S-protein and ACE2,
preventing the virus from invading host cells (Figure 1A and
B).
However, most antibodies are designed against early strains,
and the persistent mutation of SARS-CoV-2 poses challenges
for antibody efficacy and novel antibody development. As a key
site for receptor binding and antibody targeting, mutations in
the RBD can directly affect the ability of the virus to invade the
human body and change epitopes. Many variants exhibit
stronger virulence and infectivity6,14−16 and even produce
immune escape.17−22 It is urgent to investigate whether the
current epidemic lineages can escape existing antibodies.
As the two most popular mutation strains recently, Delta
(lineage B.1.617.2) and Omicron (lineage B.1.1.529) have
become the focus of many researchers.17,23−28 Since its
appearance in India in October 2020, the Delta variant has
spread to more than 185 countries and was listed as a variant
of concern (VOC) by the World Health Organization (WHO)
on May 11, 2021.29 There are two mutations, L452R and T478
K, on its RBD (Figure 1C), which can enhance the affinity
between the virus and ACE2 and trigger immune escape.30−32
Compared with the Delta variant, the Omicron variant
appeared much later, but this did not affect its rapid spread.
Since the Omicron variant was first detected on November 9,
2021, it was classified as a VOC by the WHO in just half a
month, and it has become prevalent in most regions of the
world.29 More importantly, it has an astonishing 15 mutations
on its RBD (G339D, S371L, S373P, S375F, K417N, N440K,
G446S, S477N, T478K, E484A, Q493R, G496S, Q498R,
N501Y, and Y505H) (Figure 1C). As for other VOCs, only
Received: March 30, 2022
Accepted: June 23, 2022

© XXXX American Chemical Society https://doi.org/10.1021/acs.jpclett.2c00912

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Figure 1. (A) The action mode of monoclonal antibodies (mAbs) hinders SARS-CoV-2 invasion into host cells. (B) Binding sites of the two mAbs
(Bamlanivimab and Etesevimab) to RBD. (C) The mutation residues of the SARS-CoV-2 Delta and Omicron variants in the RBD are green and
orange, respectively, and the binding sites of mAbs to the RBD are marked with dashed ellipses.
one (N501Y) in the Alpha variant, three (K417N, E484K, and
N501Y) in the Beta variant, three (K417T, E484K, and
N501Y) in the Gamma variant, and two (L452R and T478K)
in the Delta variant, the Omicron variants essentially contain
their mutation sites except for L452. This suggests that
Omicron variants may have unprecedented infection and
immune evasion capabilities, further accelerating the spread of
the epidemic.
Through the tireless efforts of scientists, some recent studies
have evaluated the effects of the Delta and Omicron variants
on Bamlanivimab and Etesevimab. The results show that the
Delta variant can escape Bamlanivimab but is still inhibited by
Etesevimab, while the Omicron variant has obvious immune
escape to both antibodies.33−36 These studies provide
experimental guidance for the subsequent use and research
of mAbs. However, the molecular mechanism of their
interaction and escape remains to be improved, especially
the identification of the key sites where the antibody-binding
epitope changes due to mutation, which is helpful for the
improvement of the design of mAbs.
In our work, molecular dynamics (MD) simulations were
used to study the binding and escape mechanisms of the Delta
and Omicron variants to Bamlanivimab and Etesevimab.
Detailed energetic and conformational analyses were used to
determine the origin of the binding differences caused by the
mutations. For the binding free energy calculation, the
enthalpy term was calculated by the molecular mechanics/
generalized Born surface area (MM/GBSA) method,37,38 and
the entropy was obtained by the interaction entropy (IE)
method.39 In addition, alanine scanning combined with the IE
(ASIE) method was used to calculate the contribution of
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individual residues to the binding affinity for key site
prediction.40−42 It is hoped that our work will provide timely
theoretical insights into the development of vaccines and
antibodies against Delta or Omicron and future novel variants.
To complement the existing experimental results from the
molecular level, a total of six systems (Bamlanivimab−WT/
Delta/Omicron and Etesevimab−WT/Delta/Omicron) were
used for the MD simulations. All systems were in a stable
binding state during the simulation with the root mean square
deviation (RMSD) fluctuating almost below the 4 Å range
(Figure S1A). When binding to Bamlanivimab, both variants
exhibited higher flexibility compared to the wild type (WT),
especially the Bamlanivimab−Omicron system, which was
significantly more flexible at the binding interface than the
other two systems (Figure S1B). When binding to Etesevimab,
all systems exhibited similar flexibility in the binding interface
(Figure S1C). The slightly higher flexibility is reflected in the
binding interface of the antibody in the Etesevimab−Omicron
complex.
Then, the binding free energy of each system was calculated
by MM/GBSA and IE methods (Table S1), and the results
were consistent with recently reported experimental evidence.
Taking the randomness into account, two repeated simulations
were performed additionally for each system, and the binding
affinity was calculated by the same method. showing that three
independent simulations obtained similar results. That is, the
Omicron variant has significantly weaker binding free energy
with both mAbs compared to the WT, while the Delta variant
only exhibits lower binding affinity to Bamlanivimab, and its
binding affinity with Etesevimab has no significant change
compared to WT. In addition, the standard error of the mean
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Figure 2. (A) Two-dimensional eigenvector projections and (B) characteristic dynamic fluctuations of the Bamlanivimab−RBD and Etesevimab−
RBD complexes. The WT, Delta, and Omicron systems are shown in blue, green, and orange, respectively.
for the binding free energy of each system was calculated
(Table S1), and the results showed that the error was too small
compared to the energy change caused by the mutations to
affect the conclusion. From each energy term, we found that
both the Delta and Omicron variants can significantly weaken
the electrostatic interaction between the RBD and mAbs. This
may be due to the mutations introducing plenty of positively
charged amino acids (L452R and T478K for Delta; N440K,
T478K, Q493R, Q498R, and Y505H for Omicron) while
reducing the number of negatively charged amino acids
(E484A for Omicron) so that more positive charges
accumulated in the binding interface (Figure S2), which
enhanced the electrostatic repulsion between the RBD and
mAbs. In addition, the Omicron variant can weaken the van
der Waals (vdW) interaction energy between the RBD and
mAbs. This may be due to the obvious changes in the
conformation and binding mode caused by the multisite
mutation of the Omicron variant, leading to fewer atomic
contacts at the binding interface. The heavy-atom contacts
between the RBD and mAbs for different distance cutoffs in
each system are calculated and support this speculation (Figure
S3).
Quantitative calculation initially reveals the energy origin of
the affinity change of each system, and the subsequent analysis
of essential dynamics was used for the in-depth exploration of
mutation-induced changes in the binding mode. The dynamic
conformational sampling of each system is projected onto the
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first two eigenvectors (Figure 2A), and it is clear that the
Bamlanivimab−Delta, Bamlanivimab−Omicron, and Etesevi-
mab−Omicron complexes have a more dispersed distribution
than the WT system, suggesting that they have lower structural
stability affected by the mutation. Then, the characteristic
dynamic fluctuations of each complex are depicted by the
maximum and minimum eigenvalues of the lowest frequency
principal component (Figure 2B). The result shows that all
complexes are deflected to varying degrees around the
interaction interface; the deflection angle is determined by
the center of mass of the mAb of the structure corresponding
to the maximum/minimum eigenvalue and the center of mass
of the RBD. The Omicron variant has the highest rotational
degrees of freedom of all systems, while the Delta variant
exhibits greater torsion than the WT only when bound to
Bamlanivimab. These changes further indicate that the
structural stabilities of the Bamlanivimab−Delta, Bamlanivi-
mab−Omicron, and Etesevimab−Omicron systems were
reduced, supporting the results of the energy calculations.
Following the assessment of the global motion patterns, the
local conformational transitions at the binding interface are
discussed via changes in the distances of each residue between
the RBD and the antibody (Figure S4). We define ΔD as the
difference between the average distance for the Cα atoms of
each residue in the equilibrium phase of the MD simulation
and the original distance in the initial structure. Negative and
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Figure 3. (A) Number and occupancy of the hydrogen bonds formed at the interaction interface. (B) Stable hydrogen bonds (occupancy ≥70%) of
each complex, marked with green dashed lines.
positive values indicate closer or farther motion between
residues, colored blue and red, respectively.
In the Bamlanivimab−RBD system, the distance change of
the Delta variant is significantly different from that of the WT
(Figure S4A and B). In the regions corresponding to 444−
455@RBD (the region where the L452R mutation is located)
and 488−501@RBD, the Delta variant has closer contact with
the light chain and residues 100−110 of the heavy chain of
Bamlanivimab than the WT, but the distance from residues
28−65 of the heavy chain of Bamlanivimab is farther than that
of the WT. Through the structural observation of the
Bamlanivimab−RBD complex (Figure S5A), we found that
100−110@Bamlanivimab is an independent region extending
from the heavy chain, located between the light chain and the
RBD. The Delta variant is close to this region while being away
from the main part of the heavy chain (residues 28−65), which
may reduce the contact area of the heavy chain with the RBD,
resulting in a more unstable binding state.
In addition, residues 444−455 and 488−501 of the Delta
variant were close to the light chain of Bamlanivimab, but the
minor changes did not play a significant role compared to the
greater distance between them. For the region near the T478K
mutation, the area closest to the light chain of Bamlanivimab
on the RBD, the Delta variant showed a tendency to move
away from the light chain in this region. This would impair the
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binding of the two, further reducing the potency of the
antibody. As for the Bamlanivimab−Omicron complex, it
showed more red patches in the image than the WT (Figure
S4C), especially in the region corresponding to the RBD and
the antibody heavy chain, indicating that more residues
separated from each other at the binding interface. This may
result in fewer atomic contacts between the RBD and the
antibody (Figure S3A), thereby exacerbating the escape of the
Omicron variant to Bamlanivimab.
The Etesevimab−Delta and Etesevimab−WT systems
showed similar distance changes (Figure S4D and E), which
was consistent with the results of energy calculations that their
binding free energies are similar. This implies that the
Etesevimab work with the virus is less affected by the Delta
variant and can still exert a neutralizing effect. As for the
Etesevimab−Omicron system (Figure S4F), more large-area
red patches appear compared to the WT. Although the part of
region corresponding to 453−493@RBD appears blue, most of
the other residues show a tendency to move away from the
binding interface, resulting in fewer atomic contacts between
Etesevimab and the Omicron RBD (Figure S3B). Through
structural analysis of the complex (Figure S5B), we found that
453−493@RBD is a long loop region close to Etesevimab,
while other regions of the RBD show a trend away from
Etesevimab. This may cause these regions away from the
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Figure 4. Binding free energy contribution of the important sites of the (A) Bamlanivimab−RBD and (B) Etesevimab−RBD complexes obtained
by the ASIE method. The energy difference between the mutant system and the WT system (ΔΔGVar−WT) is projected on the protein structure and
residues with |ΔΔGVar−WT| ≥ 1 are labeled in the images.
antibody to drag 453−493@RBD and, thus, prevent it from
approaching Etesevimab in subsequent movements, further
promoting the escape of the Omicron variant to Etesevimab.
Next, hydrogen bond network analysis was used to further
evaluate the differences in binding modes resulting from the
mutation-induced conformational changes (Figure 3A and B).
Bamlanivimab−Delta and Bamlanivimab−Omicron have more
low-occupancy hydrogen bonds (occupancy <70%) but fewer
high-occupancy hydrogen bonds (occupancy ≥70%) com-
pared to the WT, especially for the Omicron variant, which has
only one stable hydrogen bond. This may be since the
conformational transition induced by the mutation interferes
with the normal contact between Bamlanivimab and the RBD,
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thereby reducing the stability of the hydrogen bond network.
Interestingly, more stable hydrogen bonds were formed
between residues S494@RBD and E102@Bamlanivimab in
the Bamlanivimab−Delta complex compared to the WT.
According to the above analysis, this is due to the fact that
residue E102 is located in the region where the heavy chain of
Bamlanivimab extends (100−110@Bamlanivimab), and the
Delta variant has closer contacts to this region. But with the
separation between the RBD and the Bamlanivimab heavy
chain main part, the occupancy of hydrogen bonds between
residues E484@RBD and R50, R96@Bamlanivimab decreases.
The Delta variant still has fewer high-occupancy hydrogen
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Figure 5. (A) Binding free energy calculated by the MM/GBSA and IE methods. (B) Average number of heavy-atom contacts between the RBD
and mAb when the distance cutoff is set to 4−10 Å. (C and D) Superposition of the average structure of the complexes with the initial structure for
Bamlanivimab/Etesevimab−WT/Omicron systems in the equilibrium phase of the 1.5 μs MD simulation.
bonds compared to the WT; this results in the reduction of the
binding stability between the RBD and Bamlanivimab.
Both the Etesevimab−Delta and Etesevimab−Omicron
systems have more low-occupancy hydrogen bonds than the
Etesevimab−WT system. For high-occupancy hydrogen bonds,
the stable hydrogen bond originally formed between residues
R457@RBD and S53@Etesevimab in the WT system has
decreased occupancy in the Delta system, but this phenom-
enon is compensated by the hydrogen bond formed between
residues R403@RBD and Y92@Etesevimab so that Etesevi-
mab−Delta and Etesevimab−WT have the same number of
high-occupancy hydrogen bonds. As for the Omicron variant,
the two hydrogen bonds involving residues R403@RBD and
Y473@RBD become more unstable compared to the WT. This
implies that the Delta variant may have less effect on the
hydrogen bond network between Etesevimab and the RBD,
while the more unstable hydrogen bond network exhibited by
the Omicron variant may facilitate its escape from Etesevimab.
Then, the contributions of binding free energy for these
residues near the binding interface were calculated using the
ASIE method (Figure 4 and Table S2), and they are generally
considered important sites for mutation-induced changes in
the binding affinity of the system. We define these residues
with an absolute value of the binding free energy difference
from the WT system ≥1 kcal/mol as hot-spot residues. In the
Bamlanivimab−Delta complex, mutated residue 478 has a
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relatively obvious energy change, which is due to its mutation
from neutral threonine to positively charged lysine, enhancing
the electrostatic repulsion between the antibody and the RBD.
Residues Q493 and S494 in Bamlanivimab−Delta are also
more sensitive to mutation, which may be related to their
proximity to the 100−110@Bamlanivimab region.
For the Bamlanivimab−Omicron system, it has more hot-
spot residues than Bamlanivimab−Delta, probably due to the
larger number of mutation sites of the Omicron variant.
According to the results, these hot-spot residues mainly come
from those that involve the mutation of charged amino acids,
such as K417N, N440K, T478K, E484A, Q493R, and Q498R.
The residues mutated to positively charged amino acids can
induce attenuated electrostatic interaction energy, whereas
mutations to negative do the opposite. In addition, residues
V483 and F490 exhibit significant energy reduction; the former
is mainly due to weakened electrostatic energy and enhanced
polar solvation energy, and the latter comes from weakened
vdW energy.
Etesevimab−Delta and Etesevimab−WT have similar bind-
ing modes, differing only slightly in residues 403 and 478. This
may be since the charged residues introduced by the mutation
are not close to the binding interface and do not cause a
significant effect on the binding affinity. For the Etesevimab−
Omicron complex, residues 417 and 478 have obvious energy
changes among the mutated residues, both of which have
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weakened electrostatic interaction energy after mutation,
which is not conducive to their interaction with the mAbs.
Other residues involved in the mutation also have changes in
the electrostatic interaction energy, but they are offset by the
polar solvation energy, resulting in no obvious change in the
affinity of these residues with the antibody. Furthermore,
residues E406, R408, Y421, and N460 show obvious sensitivity
to mutation. They clustered in a similar region, suggesting that
large conformational changes may have occurred in this region,
leading to significant energy changes in nearby residues.
As the epidemic progresses, the Omicron variant gradually
replaces other mutant strains as the overwhelmingly dominant
variant. To verify the reliability of the above findings and to
further elucidate the escape mechanism of Omicron variants to
mAbs, we extend the MD simulation of the Bamlanivimab/
Etesevimab−Omicron systems to 1.5 μs. For comparison, the
WT systems are also extended to the same time scale.
It is found that the RMSD of each system consistently
fluctuated within a reasonable range and eventually stabilized
around 4 Å (Figure S6A), indicating that the binding mode of
mAbs−RBD stabilized and the systems had converged. The
Bamlanivimab/Etesevimab−Omicron complexes have higher
flexibility of residues near the binding interface than the WT
systems (Figure S6B and C), suggesting that the Bamlanivi-
mab/Etesevimab−Omicron systems had undergone a pro-
nounced conformational shift that may trigger an unstable
binding pattern between the RBD and the mAbs; this point is
also confirmed by the following computation.
The binding affinity of the Omicron variant to Bamlanivi-
mab/Etesevimab remains significantly weaker than that of the
WT (Figure 5A). The difference mainly arises from the
dramatic diminution in the electrostatic and vdW energies
(Table S3); the former is caused by the large number of
positively charged residues introduced through the mutation,
and the latter comes from the unstable binding mode between
the mutated RBD and the mAbs with fewer atomic contacts
(Figure 5B). These are consistent with the 100 ns conclusions.
The lowest frequency principal component is then used to
describe the characteristic dynamic fluctuations of each system
(Figure S7). Their dynamic characteristics are found to be
similar to the results above; that is, the mAbs deflect on the
axis of the binding interface, and the Omicron variant exhibits
greater rotational freedom than the WT, suggesting unstable
binding of the Omicron variant to the mAbs compared to the
WT.
Subsequently, the distance changes between residues near
the binding interface are calculated for further elaboration of
the escape trend of the Omicron variant toward Bamlanivi-
mab/Etesevimab (Figure S8). Apparently, the distribution of
the distance changes of WT systems is similar to that of the
100 ns simulation, indicating that the WT is still stably binding
to the mAbs. However, a large dark red patch appears in the
Omicron variant systems, suggesting that it is away from the
mAbs, resulting in less atomic contact and hydrogen bonding
between the two (Figure S9).
Interestingly, although the Omicron variant exhibits a more
unfavorable binding mode to the mAbs compared to the WT,
there are still a few blue patches (Figure S8). To visualize the
escape pattern of the Omicron variant toward mAbs, the
average conformation of the equilibrium phase is used for
comparison with the initial structure (Figure 5C and D). We
find that the average structures of the Bamlanivimab/
Etesevimab−WT systems are similar to the initial structure
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with minor differences, which are not sufficient to affect the
sustained stabilization of the mAbs against the WT. In contrast,
for the Bamlanivimab/Etesevimab−Omicron complexes, there
is a significant deflection from the initial structure. The
conformational change leads to an open hinge-like angle
between the binding interface of the mAbs and the RBD, with
one side of the mAbs gradually moving away from the RBD
while the other side is temporarily immobile or slightly closer
to the RBD. This explains why the Omicron variant shows a
large number of red patches but still retains a few blue patches
(Figure S8). However, with a gradual increase of the opening
angle, the contact between mAbs and the RBD becomes less
and less; the RBD will get rid of the mAbs’ grasp on it, thus
producing the immune escape.
In summary, we dissect the impact of recently circulating
SARS-CoV-2 Delta and Omicron mutant strains on
Bamlanivimab and Etesevimab, two RBD-targeting mAbs
already approved for therapy. The results show that the
Omicron variant appears to be more prone to immune escape
than the Delta variant, from both the energetic and
conformational perspectives. The Omicron variant carries
multiple mutations that, on the one hand, weaken the
electrostatic interaction between the RBD and the mAbs by
introducing a large number of positively charged amino acids.
On the other hand, it triggers a significant conformational
deflection resulting in less contact between the RBD and the
antibody, thus reducing the binding stability of both. As for the
Delta variant, the introduction of two positively charged amino
acids in the RBD also results in a weakening of the electrostatic
interaction energy between the RBD and the mAbs, but this
change is balanced by the polar solvation energy. The real
reason for the reduced affinity of the Delta variant for
Bamlanivimab is that the mutation causes the RBD to be close
to the extended region of the antibody (100−110@
banranivirumab) but away from the main part of the heavy
chain (28−55@banranivirumab). This change increases the
rotational freedom of Bamlanivimab binding to the RBD and
reduces the number of stable hydrogen bonds between the
two, leaving the complex in an unstable binding state. In
addition, the binding mode of the Delta variant to Etesevimab
is similar to that of the WT, which may be because the
mutation site is far away from the binding interface and the
presence of the mutation does not cause significant conforma-
tional changes. Our work reveals the escape mechanism of
mainstream SARS-CoV-2 variants against two mAbs that
received EUA at the molecular level, which provides timely
theoretical insights for the improvement of existing antibodies
and the development of novel antibodies.
■
*
ASSOCIATED CONTENT
sı Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.jpclett.2c00912.
Research methods, RMSD and RMSF of each complex,
surface electrostatic potential distribution of the RBD
(WT, Delta, and Omicron) and mAbs (Bamlanivimab
and Etesevimab), distribution of the number of heavy-
atom contacts between the RBD and mAbs, distance
change between residues near the binding interface,
structural representations of the Bamlanivimab−RBD
and Etesevimab−RBD complexes, the RMSD, RMSF,
characteristic dynamic fluctuations, distance change, and
https://doi.org/10.1021/acs.jpclett.2c00912
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The Journal of Physical Chemistry Letters
hydrogen bonds of the Bamlanivimab/Etesevimab−
WT/Omicron systems for the 1.5 μs MD simulation,
the binding free energy of each system calculated by the
MM/GBSA and IE methods, and the energy terms of
the binding free energy for each residue obtained by the
ASIE method (PDF)
■ AUTHOR INFORMATION
Corresponding Authors
John Z. H. Zhang − Shanghai Engineering Research Center of
Molecular Therapeutics and New Drug Development, School
of Chemistry and Molecular Engineering, East China Normal
University, Shanghai 200062, China; Shenzhen Institute of
Synthetic Biology, Shenzhen Institute of Advanced
Technology, Chinese Academy of Sciences, Shenzhen 518055,
China; NYU-ECNU Center for Computational Chemistry at
NYU Shanghai, Shanghai 200062, China; Department of
Chemistry, New York University, New York, New York
10003, United States; orcid.org/0000-0003-4612-1863;
Email: john.zhang@nyu.edu
Lili Duan − School of Physics and Electronics, Shandong
Normal University, Jinan 250014, China; orcid.org/
0000-0002-1293-6784; Email: duanll@sdnu.edu.cn
Authors
Danyang Xiong − School of Physics and Electronics, Shandong
Normal University, Jinan 250014, China; orcid.org/
0000-0002-0911-1888
Xiaoyu Zhao − School of Physics and Electronics, Shandong
Normal University, Jinan 250014, China
Song Luo − School of Physics and Electronics, Shandong
Normal University, Jinan 250014, China
Yalong Cong − Shanghai Engineering Research Center of
Molecular Therapeutics and New Drug Development, School
of Chemistry and Molecular Engineering, East China Normal
University, Shanghai 200062, China; orcid.org/0000-
0002-0910-811X
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.jpclett.2c00912
Notes
The authors declare no competing financial interest.
■ ACKNOWLEDGMENTS
This work was supported by the National Natural Science
Foundation of China (Grant nos. 21933010 and 11774207)
and the NYU-ECNU Center for Computational Chemistry at
NYU Shanghai. We thank the ECNU Public Platform for
Innovation 001 for providing supercomputer time.
■
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