Structure and Dynamics of Confined Water Inside Diphenylalanine Peptide Nanotubes

Diphenylalanine (FF) peptides exhibit a unique ability to self-assemble into nanotubes with confined water molecules playing pivotal roles in their structure and function. This study investigates the structure and dynamics of diphenylalanine peptide nanotubes (FFPNTs) using all-atom molecular dynamics (MD) and grand canonical Monte Carlo combined with MD (GCMC/MD) simulations with both the CHARMM additive and Drude polarizable force fields. The occupancy and dynamics of confined water molecules were also examined. It was found that less than 2 confined water molecules per FF help stabilize the FFPNTs on the x–y plane. Analyses of the kinetics of confined water molecules revealed distinctive transport behaviors for bound and free water, and their respective diffusion coefficients were compared. Our results validate the importance of polarizable force field models in studying peptide nanotubes and provide insights into our understanding of nanoconfined water

Binding Energy and Free Energy of Calcium Ion to Calmodulin EF-Hands with the Drude Polarizable Force Field

Calcium ions are important messenger molecules in cells, which bind calcium-binding proteins to trigger many biochemical processes. We constructed four model systems, each containing one EF-hand loop of calmodulin with one calcium ion bound, and investigated the binding energy and free energy of Ca2+ by the quantum mechanics symmetry-adapted perturbation theory (SAPT) method and the molecular mechanics with the additive CHARMM36m (C36m) and the polarizable Drude force fields (FFs). Our results show that the explicit introduction of polarizability in the Drude not only yields considerably improved agreement with the binding energy calculated from the SAPT method but is also able to capture each component of the binding energies including electrostatic, induction, exchange, and dispersion terms. However, binding free energies computed with the Drude and the C36m FFs both deviated significantly from the experimental measurements. Detailed analysis indicated that one of main reasons might be that the strong interactions between Ca2+ and the side chain nitrogen of Asn/Gln in the Drude FF caused the distorted coordination geometries of calcium. Our work illustrated the importance of polarization in modeling ion–protein interactions and the difficulty in generating accurate and balanced FF models to represent the polarization effects