Table 2.
Comparison of hACE2 mutations that show enhanced RBD binding from experiments and computational predictions.
| hACE2 residues | Point mutations to amino acids that show enhanced binding with RBD experimentally **(log2 enrichment ratio) |
Computationally predicted hACE2 variants that improve binding to RBD |
||
|---|---|---|---|---|
| Single # (ΔGwt kcal/mol) ↑ |
Double # (ΔGwt kcal/mol) ↑ |
Triple # (ΔGwt kcal/mol) ↑ |
||
| S19 | P > F > Y > W > V (2.1 > 1.2 > 1.1 > 1.1 > 1.1) |
P* > F* > L (2.3 > 2.0 > 1.9) |
S19K + T20H > S19K + T20E (2.4 > 2.2) |
S19K + T20H + I21T > S19K + T20H + E22Q (3.2 > 2.9) |
| T20 | S > E (0.1 > 1.0) |
S* > D > E* (0.5 > 0.3) |
S19K + T20H > S19K + T20E (2.4 > 2.2) |
S19K + T20H + I21T > S19K + T20H + E22Q (3.2 > 2.9) |
| I21 | V > G > T (0.7 > 0.2 > 0.2) |
L > V* (1.2 > 0.8) |
none | S19K + T20H + I21T (3.2) |
| E22 | T > Q > D (1.1 > 0.6 > 0.5) |
Q* > S (1.6 > 1.2) |
none | S19K + T20H + E22Q (2.9) |
| E23 | F > C > M > Q (2.1 > 0.9 > 0.8 > 0.8) |
Y* > F > T (2.2 > 2.0 > 1.9) |
none | None |
| Q24 | T > P (1.8 > 0.1) |
S > T* (2.0 > 1.2) |
none | None |
| A25 | V > T > F > I (2.8 > 1.4 > 1.2 > 1.1) |
S > T* > L (3.2 > 3.1 > 2.2) |
none | None |
| K26 | D > I > V > A > R (2.2 > 1.7 > 1.4 > 1.4 > 1.3) |
D* > E > R* (2.0 > 1.8 > 1.8) |
none | None |
| T27 | Y > L > M > H (2.8 > 2.8 > 2.4 > 2.2) |
S > M* > W > A (3.4 > 3.1 > 1.9 > 1.3) |
T27I + F28D (2.1) |
None |
| F28 | Y (0.8) |
Y* > V (1.2 > 0.4) |
F28Y + D30E > F28D + L29E > T27I + F28D (2.8 > 2.4 > 2.1) |
None |
| L29 | F > E (1.9 > 0.15) |
T > F* (2.3 > 2.1) |
F28D + L29E > L29F + D30I > L29E + A36E (2.4 > 2.2 > 2.1) |
None |
| D30 | E > I > V > T (2.3 > 1.7 > 1.3 > 0.8) |
E* > V* > T* (2.5 > 2.1 > 1.2) |
F28Y + D30E > L29F + D30I (2.4 > 2.2) |
None |
| K31 | W > Y > F (2.6 > 2.0 > 0.8) |
R > W* (3.1 > 1.4) |
none | None |
| F32 | not reported | A > E (2.5 > 1.9) |
F32E + A36E (2.1) |
F32E + A36E + D37P (2.7) |
| N33 | D > E > H > S (1.9 > 0.8 > 0.8 > 0.8) |
E* > D* > H* (1.3 > 1.2 > 1.1 > 1.1) |
none | None |
| H34 | V > A > P > S > W (2.8 > 2.7 > 2.6 > 1.7 > 0.3) |
S* > T > G (3.2 > 3.1 > 2.2) |
H34V + E35D (2.2) |
None |
| E35 | C > D > M > A (1.8 > 1.4 > 1.2 > 0.7) |
D* > M* > V (1.5 > 1.2 > 1.1) |
H34V + E35D (2.2) |
None |
| A36 | not reported | E > S (2.4 > 2.1) |
L29E + A36E > F32E + A36E (2.1 > 2.1) |
F32E + A36E + D37P > A36E + D37P + D38E (2.7 > 2.7) |
| E37 | P (0.9) |
V > P* > A (1.9 > 1.8 > 1.4) |
none | F32E + A36E + D37P > A36E + D37P + D38E (2.7 > 2.7) |
| D38 | E (0.3) |
E* > S (1.2 > 1.0) |
none | A36E + D37P + D38E (2.7) |
| L39 | K > R > I > V > A (2.3 > 2.2 > 1.4 > 1.1 > 1.0) |
R* > K* (2.7 > 2.1) |
L39A + F40H (2.3) |
None |
| F40 | D > R > K > C > H (1.7 > 1.5 > 1.3 > 0.9 > 0.13) |
E > R* (2.0 > 1.8) |
L39A + F40H (2.3) |
F40E + Y41A + Q42K > D40E + Y41A + Q42K (2.8 > 2.3) |
| Y41 | R (1.7) |
F > R* (2.2 > 2.1) |
Y41A + Q42K (2.2) |
F40E + Y41A + Q42K > D40E + Y41A + Q42K (2.8 > 2.3) |
| Q42 | C > L > M > V > I (2.8 > 2.6 > 2.4 > 1.9 > 1.7) |
M* > V* > I* > L* (3.1 > 2.8 > 2.2 > 1.7) |
Y41A + Q42K (2.2) |
F40E + Y41A + Q42K > F40D + Y41A + Q42K (2.8 > 2.3) |
| Q325 | P > K (2.7 > 2.0) |
K* > R (2.8 > 2.2) |
none | Q325K + G326E + A387H > Q325K + G354A + D355E (2.7 > 2.6) |
| G326 | E (1.3) |
D > E* (2.6 > 2.2) |
none | Q325K + G326E + A387H (2.7) |
| K353 | none | none | none | none |
| G354 | none | A (2.4) |
none | Q325K + G354A + D355E (2.6) |
| D355 | none | E (1.7) |
none | Q325K + G354A + D355E (2.6) |
| A387 | H (1.4) |
Q > H* (1.1 > 0.4) |
none | Q325K + G326E + A387H (2.7) |
**log2 enrichment ratios reflect increase in experimentally binding affinity with RBD upon point mutation with respect to wild-type. ^ Increase in RBD binding energy (in kcal/mol) of an hACE2 variant with respect to WT hACE2. * RBD-binding enhancing hACE2 mutations identified from experiments which were recovered from in silico predictions as well.