Non-peptidic segments that can be employed as �-strand mimetics have received attention due to their potential to disrupt protein � protein interactions. Sulfonamides are of interest as their adjacent S=O and N-H moieties allow for extensive hydrogen bonding with the environment. To study the conformational behavior of such systems, the CHARMM General force field (CGenFF) was extended to enable the modeling of sulfonamide moieties. Target data included quantum mechanical and experimental crystal data, with the developed parameters validated against crystalline and liquid phase experimental data. The CGenFF parameters were then combined with the CHARMM protein FF to perform temperature replica exchange molecular dynamics on a sulfonamide containing peptide. The model was able to capture the experimentally observed conformations and the predicted hydrogen bonding patterns were in good accordance with the experimentally determined chemical shifts. This study shows that CGenFF can be combined with the CHARMM biomolecular FF in biomolecular simulations.

Conformational behavior of a sulfonamide containing peptide studied using the CHARMM general force field

244th National Meeting (2012)

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