The accuracy of the determination of the energy of interaction between Phe20 and the Pro5-Thr6-Tyr7-Pro8 complex inside the hydrophobic core of avian pancreatic polypeptide was investigated using three capping strategies for molecular fractionation with conjugated caps and DFT quantum chemical calculations at the BHandHLYP/cc-pVTZ level of theory. The most accurate determination resulted from acetylation of the α-amino group combined with methyl amidation of the α-carbonyl group, with relative deviations less than 10%. Combinations of hydrogenation of the α-amino group with the replacement of the α-carbonyl group with a hydrogen and the hydrogenation of the α-amino group with methylation of the α-carbonyl group were less accurate, leading to relative deviations up to 35%. Choice of capping methods depends on the structural features of the polypeptide system, the desired accuracy, and the available computational resources.
All Science Journal Classification (ASJC) codes
- Atomic and Molecular Physics, and Optics
- Condensed Matter Physics
- Physical and Theoretical Chemistry