TABLE 6.
Knowledge-based energies of a representative lexitropic polyamide bound to sequence-modified DNA
| Energies
|
||||||||
|---|---|---|---|---|---|---|---|---|
| Clustering
|
Local density
|
Global density
|
||||||
| Sequence* single-base substitution | Comp_ID* | Steric hindrance | ETot | ΔETot | ETot | ΔETot | ETot | ΔETot |
| bdd002 | ||||||||
| CCAGTACTGG | 62.3 | 38.2 | 35.8 | |||||
| ---C------ | (S1a) | † | 5.0 | −0.3‡ | 0.9 | |||
| ----A----- | (S1b) | 10.2 | 10.2 | 8.5 | ||||
| -----T---- | (S1c) | 8.0 | 5.6 | 7.9 | ||||
| ------G--- | (S1d) | § | 3.2 | 2.8 | 3.6 | |||
| ---A------ | (S1m) | 21.8 | 25.4 | 22.2 | ||||
| ----C----- | (S1n) | § | 7.7 | −0.7 | 1.1 | |||
| -----C---- | (S1o) | § | 0.4 | 0.5 | 1.6 | |||
| ------A--- | (S1p) | 28.4 | 22.7 | 25.0 | ||||
| ---T------ | (S1w) | 25.7 | 21.4 | 23.1 | ||||
| ----G----- | (S1x) | § | 8.5 | 2.5 | 4.8 | |||
| -----G---- | (S1y) | § | 4.7 | −3.1 | −0.2 | |||
| ------T--- | (S1z) | 22.6 | 25.3 | 23.2 | ||||
*
Only one of the two DNA strands is listed for each drug-DNA structure. Comp_ID is the identification code of the computer substitution experiment referenced in the text.
†
Steric hindrance that is predicted to occur in the drug design (Kielkopf et al., 1998a,b, 2000; White et al., 1998), is not detected. Such situations occur only when Im·Py drug pairs are used to recognize G·C basepairs.
‡
Basepair substitution results are inconsistent with predictions, i.e., the basepair change neither increases the total energy nor introduces steric hindrance.
§
Steric hindrance exists between the ligand and modified DNA.