Theoretical Computational Analysis Predicts Interaction Changes Due to Differences of a Single Molecule in DNA

Theoretical methods, such as molecular mechanics and dynamics, are very useful in understanding differences interactions at the single molecule level. In life sciences, small conformational changes, including substituent modifications, often have a significant impact on function vivo. Changes binding between nucleic acid molecules proteins prime example. this study, we propose strategy to predict complex structure of DNA-binding with arbitrary DNA analyze their interactions. We tested utility our using anticancer drug trifluoro-thymidine (FTD), which exerts its pharmacological effect by incorporation into DNA, confirmed that affinity BCL-2-associated X sequence p53 tetramer is increased FTD incorporation. On contrary, p53-binding sequences extracted from FTD-resistant cells, containing was found be greatly reduced compared normal DNA. This suggests thymidine randomly substituted for resistant cells may acquire resistance entering position inhibits proteins. believe versatile procedure can also take energetics account will increase importance computational science sciences.