Table 2. Calculated Binding Energies, Ligand Efficiencies, and Binding Modes of Synthesized Compounds to CHIKV nsP2.
| binding site 1 |
binding site 2 |
||||||
|---|---|---|---|---|---|---|---|
| code | absolute configuration of stereocenters | ΔG (kcal/mol) | LEa | interactions (H-bonds) | ΔG (kcal/mol) | LEa | interactions (H-bonds) |
| D27 | S,S,S | –9.1 | 0.35 | Cys1013, Ala1046, Tyr1079 (HO···HN, HO···H2N), Asn1082 (O(carbonyl)···H2N), Trp1084, Leu1205 | –8.0 | 0.30 | Gln1039, Lys1045, Leu1203, Glu1204 (COO–···H2N), Pro1224, Asp1235, Lys1239 |
| D119 | S,S,S | –9.0 | 0.31 | Cys1013, Ala1046, Tyr1079, Asn1082, Trp1084, Leu1205 | –6.9 | 0.23 | Lys1045, Pro1191, Glu1204, Ile1221, His1222, Pro1224, Lys1239, Met1242, Leu1243 |
| D127 | S,S,S | –9.0 | 0.31 | Cys1013, Ala1046, Tyr1079 (HO···HN, HO···H2N), Asn1082 (O(carbonyl)···H2N), Trp1084, Leu1205 | –8.5 | 0.29 | Gln1039, Lys1045, Leu1203, Glu1204 (COO–···H2N), Ile1221, Pro1224, Asp1235, Lys1239, Leu1243 |
| D159 | S,S,S | –7.1 | 0.19 | Asn1011, Cys1013, Ser1048, Tyr1079 (HO···HN), Asn1082, Trp1084, Leu1205, Gln1241, Met1242, Asp1246 | –7.5 | 0.20 | Lys1045, Pro1191, Val1194, Leu1203, Glu1204, Lys1239, Leu1243 |
| D160a | R,R,S | –8.8 | 0.27 | Tyr1079, Asn1082, Trp1084, Lys1091, Met1242 | –9.0 | 0.27 | Pro1191, Leu1203, His1222, Lys1239 |
| D160b | R,R,R | –7.6 | 0.23 | Ser1048, Tyr1079 (HO···HN(substituted terminal group)), Trp1084, Lys1091, Met1242, Asp1246 | –8.8 | 0.27 | Lys1045, Pro1191, Leu1203, Ile1221, His1222, Met1238, Lys1239 |
| D160c | S,S,R | –8.0 | 0.24 | Asn1011, Cys1013, Ala1046, Tyr1047, Tyr1079, Asn1082, His1083, Trp1084, Asn1202, Glu1204, Leu1205 | –9.2 | 0.28 | Lys1045, Pro1191, Leu1192, Leu1203, Ile1221, His1222, Lys1239, Leu1243 |
| D160d | S,S,S | –8.8 | 0.27 | Cys1013, Ala1046, Tyr1079 (HO···HN, HO···HN(substituted terminal group)), Asn1082 (O(carbonyl)···HN(substituted terminal group)), Trp1084, Leu1205, Met1242 | –8.9 | 0.27 | Pro1191, Leu1192, Leu1203 (NH(peptide)···O(carbonyl)), Glu1204, Met1238, Lys1239, Met1242 |
| D161 | S,S,S | –7.6 | 0.25 | Asn1011, Cys1013, Ala1046, Tyr1079, Asn1082, Trp1084, Asn1202, Glu1204, Leu1205, Met1242 | –7.6 | 0.25 | Gly1176, Pro1191, Ile1221, His1222, Lys1239, Leu1243 |
| D162 | S,S,S | –8.2 | 0.29 | Asn1011, Cys1013, Ala1046, Tyr1047, Tyr1079, Asn1082 (O(peptide)···H2N), Trp1084, Asn1202, Glu1204, Met1242 | –7.6 | 0.27 | Lys1045, Leu1192, Leu1203, Glu1204 (COO–···H2N), Ile1221, Lys1239, Met1242, Leu1243 |
| D163 | S,S,S | –8.1 | 0.28 | Ala1046, Tyr1047, Ser1048, Tyr1079, Trp1084, Lys1091, Leu1205, Gln1241, Met1242 | –7.5 | 0.26 | Lys1045, Leu1203, Ile1221, His1222, Lys1239, Leu1243 |
| D164 | S,S,S | –8.1 | 0.26 | Ser1048, Tyr1079, Trp1084 | –8.1 | 0.26 | Pro1191, Leu1192, Leu1203 (NH···O(carbonyl)), Glu1204, Ile1221, Lys1239, Leu1243 |
| D165 | S,S,S | –8.0 | 0.21 | Cys1013, Ala1046, Tyr1047, Ser1048, Tyr1079, Asn1082, Trp1084, Gln1241, Met1242 | –8.0 | 0.21 | Lys1045, Pro1191, Val1194, Leu1203, Ile1221, Lys1239, Leu1243 |
| D166 | S,S,S | –8.4 | 0.21 | Ala1046, Tyr1079, Asn1082, Trp1084, Lys1091, Met1242 | –8.4 | 0.21 | Lys1045, Val1194, Leu1203, Ile1221, Lys1239, Leu1243 |
a
LE: ligand efficiency, that is, ΔG/N (heavy atoms).