Appendix 1—table 2. Small molecule contact frequencies.
| Amino acid sp2group* | # PDBs | # Ligand Groups |
Ligand Pi-Pi Contact Frequency (%) |
# Protein Groups |
Protein contact frequency (%) | O/E (Ligand/Protein) |
|---|---|---|---|---|---|---|
| GLU Sidechain | 84 | 209 | 16.3 ± 4.1 | 5353 | 5.0 ± 0.4 | 3.3 ± 0.8 |
| HIS Sidechain | 36 | 80 | 42.5 ± 8.0 | 530 | 17.4 ± 2.7 | 2.4 ± 0.7 |
| PHE Sidechain | 36 | 93 | 53.8 ± 9.0 | 1389 | 28.4 ± 2.3 | 1.9 ± 0.3 |
| ARG Sidechain | 61 | 145 | 43.9 ± 6.0 | 2878 | 15.9 ± 0.9 | 2.8 ± 0.5 |
| TYR Sidechain | 30 | 68 | 58.8 ± 12.2 | 806 | 19.9 ± 1.9 | 3.0 ± 0.7 |
| GLN Sidechain | 21 | 50 | 22.0 ± 8.9 | 800 | 13.0 ± 2.3 | 1.8 ± 0.8 |
| ASP Sidechain | 39 | 86 | 3.5 ± 2.0 | 2153 | 4.5 ± 0.8 | 0.8 ± 0.5 |
| TRP Sidechain | 43 | 109 | 50.5 ± 8.0 | 377 | 28.9 ± 2.3 | 1.7 ± 0.3 |
| ASN Sidechain | 11 | 32 | 6.3 ± 7.3 | 466 | 8.6 ± 1.9 | 0.7 ± 0.9 |
| Amino Carboxyl | 688 | 1704 | 8.9 ± 1.1 | 976 | 5.7 ± 1.2 | 1.5 ± 0.4 |
| Small molecule† | # PDBs | # Free Ligands |
Ligand
Pi-Pi Contact Frequency (%) |
# sp2 Atoms | RCSB Ligand ID | Isomeric SMILES |
| Ethanal | 44 | 76 | 3.9 ± 2.9 | 2 | ACE | CC = O |
| Formic Acid | 444 | 2093 | 11.0 ± 0.8 | 3 | FMT | OC = O |
| Acetate Ion | 1664 | 4794 | 12.9 ± 0.6 | 3 | ACT | CC([O-])=O |
| Acetic Acid | 403 | 1133 | 13.5 ± 1.5 | 3 | ACY | CC(O)=O |
| Nitrate Ion | 225 | 852 | 15.3 ± 1.7 | 4 | NO3 | [O-][N+]([O-])=O |
| Guanidine | 32 | 115 | 15.7 ± 4.7 | 4 | GAI | NC(N)=N |
| Urea | 23 | 91 | 16.5 ± 4.0 | 4 | URE | NC(N)=O |
| Imidazole | 279 | 684 | 26.6 ± 2.4 | 5 | IMD | C1C[NH+]C[NH]1 |
*Entries containing amino acids or small sp2 containing planar molecules as free ligands were downloaded from the PDB (filtered to maximum sequence redundancy of 90% and 3 Å resolution) and pi-pi contact frequencies for ligands and their corresponding protein based equivalents were determined.
The majority of amino acids are more likely to form pi-pi contacts to protein when found as non-covalently bound ligands, rather than as residues within a protein, confirming that pi-pi contacts are a consistent property of amino acid interactions involving protein.
†In order to avoid bias due to the constrained geometries of functional binding sites we also analyzed the contact frequencies of a variety of common buffer components, with contact frequencies found to increase with number of sp2-hybridized atoms.
Ranges show standard error of the mean.