Table 1. Important Intermolecular Polar and Nonpolar Interaction Free Energies, Hydrogen Bonds and Salt Bridges, between CXCL12 and CXCR4 Residue Pairs within the Final Simulation (see Methods)a.
| CXCL12§ | CXCR4¶ residues (polar, nonpolar interaction free energies) | salt bridgesc and hydrogen bondsd |
|---|---|---|
| Lys1 | Tyr45 (2.1, −0.6)b, Trp94 (−2.6, −2.4), Asp97 (−0.4, 0.0), His113 (−6.4, −0.9), Tyr116 (−4.1, −1.7), Asp171 (−69.9, 2.6), Arg188 (15.8, −2.9), Gln200 (−17.2, 0.7), His203 (−14.6, 0.4), Tyr255 (−0.4, −1.1), Asp262 (−0.4, −0.1), Ile284 (−1.2, −0.7), Ser285 (−1.6, −0.3), Glu288 (−79.8, 5.4) | dLys1 N: Tyr45 OH, dLys1 N: Tyr255 OH, cLys1:Glu288, dLys1 NZ: Tyr116 OH, cLys1: Asp171, dLys1 NZ: Gln200 OE1, dLys1 NZ: His203 NE2 |
| Pro2 | Trp94 (−0.1, −1.8), Asp97 (0.1, −0.8), His113 (−0.3, −0.7), Cys186 (0.1, −1.2), Asp187 (−0.3, −1.9), Arg188 (−12.4, –1.8) | dPro2 O: Arg188 NE/NH2 |
| Val3 | Arg188 (−0.1, −1.5), His281 (−0.2, −2.3), Ile284 (−0.2, –2.3) | |
| Ser4 | Arg30 (−0.1, −1.5), His281 (−0.6, –2.0) | dSer4 OG: Arg30 NH2 |
| Leu5 | Lys25 (−2.6 −1.3), Asp262 (0.4, −2.2), Ile265 (0.0, −2.1), Glu268 (0.0, −2.2), Glu277 (−0.5, −3.6), Val280 (0.2, −1.7), His281 (−0.5, –3.0) | dLeu5 O: Lys25 NZ, dLeu5 N: His281 NE2 |
| Ser6 | Cys28 (0.0, −1.7), Arg30 (−6.3, −2.9), Glu277 (−1.0, −2.6), Asn278 (−1.6, –2.0) | dSer6 OG: Arg30 NH2, dSer6 OG: Asn278 OD1 |
| Tyr7 | Pro27 (−0.1, −1.2), Cys28 (−0.2, −1.0), Arg30 (0.2, –3.4) | |
| Arg8 | Glu2 (−25.7, −0.8), Met16 (−0.1, −0.7), Asp187 (−18.1, 1.3), Arg188 (−1.3, −1.7), Phe189 (−0.7, −2.7), Tyr190 (−1.1, −2.7), Leu266 (−0.1, –0.6) | cArg8:Glu2, cArg8:Asp187, dArg8 NH2: Arg188 O |
| Cys9 | Glu2 (−5.3, –1.7) | dCys9 N: Glu2 OE* |
| Pro10 | Glu14 (0.0, −1.1), Met16 (0.0, −1.5), Met24 (−0.2,-3.0), Lys25 (0.1, −2.2), Pro27 (0.0, –0.4) | |
| Cys11 | Ile6 (0.1, −0.8), Tys7 (0.2, −0.8), Glu14(−4.4, −2.2), Met24 (−0.2, –2.1) | |
| Arg12 | Glu2 (−7.4, −0.1), Ile6 (−1.3, −1.9), Tys7 (−6.8, −4.4), Tys12 (−2.4, −1.3), Glu14 (−12.3 −1.7), Met16 (−0.6, −1.1), Tyr190 (−3.9, −2.8), Pro191 (−0.3, −2,1), Asn192 (0.9, −1.5), Asp193 (−21.8, 0.3) | dArg12 O:Tys7 N, dArg12 N: Glu14 OE2, cArg12:Glu2, cArg12:Tys7, dArg12 NH2: Met16 SD, dArg12 NH1: Tyr190 O, cArg12:Asp193 |
| Phe13 | Tys7 (−1.8, −5.4), Thr8 (−0.4, −1.5), Asp10 (0.4, −2.1), Tys12 (0.1, −4.3), Glu14 (−7.9, –1.1) | dPhe13 N: Glu14 OE2 |
| Phe14 | Ile6 (0.1, −2.4), Tys7 (−2.6, −2.0), Thr8 (−1.7 −2.5), Ser9 (−1.5, –1.2) | dPhe14 N: Tys7 O, dPhe14 N: Thr8 O, dPhe14 O: Ser9 N, dPhe14 O: Asp10 N, dPhe14 O: Asn11 N |
| Glu15 | Ser9 (−6.7, −3.2), Asp10 (−9.2, −0.8), Asn11 (−10.2, −1.2), Tys12 (−3.3, –2.0) | dGlu15 OE*: Asp10 N, dGlu15 OE*: Asn11 N, dGlu15 OE1: Tys12 N |
| Ser16 | Ser9 (−3.0, –1.2) | dSer16 N/OG: Ser9 OG |
| His17 | Asn11 (0.0, –2.3) | dHis17 ND1: Asn11 ND2 |
| Lys24 | Asp20 (−0.5, 0.0), Tys21 (−10.5, –1.2) | cLys24:Tys21 |
| His25 | Tys21 (0.0, –0.9) | |
| Lys27 | Asp20 (−0.6, 0.0), Tys21 (−0.9, −0.3), Glu26 (−5.5, −1.6), Pro27 (−0.6, –2.2) | cLys27:Glu26 |
| Leu29 | Pro27 (0.2, −2.6), Cys28 (−0.1, −2.0), Phe29 (−0.1, –2.9) | |
| Asn30 | Cys28 (0.2, −0.4), Phe29 (−0.3, −1.4), Arg30 (−0.1, –0.4) | |
| Thr31 | Pro27 (0.2, −1.6), Cys28 (0.0, −0.6), Arg30 (0.4, –0.4) | |
| Pro32 | Arg30 (0.0, −1.9), Glu32 (0.1, −0.4), Asp181 (0.0, –0.5) | |
| Asn33 | Met1 (0.1, −2.4), Glu2 (−0.7, −1.8), Glu189 (0.0, −0.5), Ala180 (−0.9, −2.2), Asp181 (−4.3, –1.5) | dAsn33 OD1/ND2: Asp181 N, dAsn33 ND2: Asp181 OD* |
| Cys34 | Met1 (0.6, −3.4), Glu2 (−0.1, –2.8) | dCys34 N: Met1 SD |
| Ala35 | Met1 (−0.2, −2.0), Ile6 (0.0, –0.9) | |
| Val39 | Met24 (−0.1, −1.7), Pro27 (0.1, –1.3) | |
| Arg41 | Asp20 (−0.6,-0.1), Tys21 (−25.1, −5.2), Asp22 (−1.5, −1.2), Ser23 (−0.9, –1.2) | dArg41 NH*: Tys21 O, cArg41:Tys21, dArg41 NH1: Ser23 OG |
| Leu42 | Thr13 (0.0, –0.4) | |
| Lys43 | Tys21 (−0.4, –0.2) | |
| Asn46 | Tys21 (−3.4, –2.5) | dAsn46 ND2: Tys21 OS* |
| Arg47 | Thr13 (−13.0, −2.5), Glu14 (−0.8, −0.6), Glu15 (−15.8, −0.2), Asp20 (−0.4, 0.0), Asp22 (−7.9, −0.8), Ser23 (−0.6, –4.9) | dArg47 NH2: Thr13 O, dArg47 NE/NH2: Thr13 OG1, cArg47:Glu15, cArg47:Asp22, dArg47 NH1: Ser23 N |
| Gln48 | Thr13 (−0.8, −1.0), Ser23 (−5.7, −0.8), Met24 (−0.8, −5.3), Lys25 (−0.6, −1.0), Glu26 (−0.1, –1.4) | dGln48 N: Ser23 OG, dGln48 O: Met24 N,dGln48 NE2: Met24 O,dGln48 NE2: Lys25 O |
| Val49 | Thr13 (0.1, −1.9), Glu14 (−0.7, −0.5), Met24 (−0.3, –2.5) | |
| Cys50 | Glu14 (1.0, −0.8), Met24 (0.1, –2.3) | |
| Asp52 | Thr8 (−0.2, −0.4), Ser9 (0.0, –0.4) |
a
CXCL12 and CXCR4 residues marked in boldface are experimentally associated with binding-signaling (see Discussion – Agreement with Experiments). The results presented correspond to analysis of 1000 snapshots of the final simulation.
b
Principal interacting CXCL12§–CXCR4¶ residue pairs. For each pair, the average polar and nonpolar average interaction free energies (polar, nonpolar) are provided in parentheses next to each CXCR4 residue; all energies are in kcal/mol.
c
Salt bridges between CXCL12 and CXCR4 residue pairs.
d
Hydrogen bonds between CXCL12 and CXCR4 atom pairs. The asterisk (*) symbol used after any CXCL12/CXCR4 atom in the hydrogen bonding pair denotes that any of the atoms in the charged, carboxyl or amide, side-chain group can participate in the hydrogen-bond formation.