Intra-protein hydrogen bonding is dynamically stabilized by electronic polarization

Area of Science:

• Computational chemistry
• Biophysics
• Structural biology

Background:

• Intra-protein hydrogen bonds are crucial for protein structure and function.
• Standard atomic charge models may not fully capture the electronic environment of proteins.
• Accurate representation of electronic polarization is essential for reliable molecular dynamics simulations.

Purpose of the Study:

• To compare the dynamical stability of intra-protein hydrogen bonds using standard AMBER charges versus polarized protein-specific charges (PPC).
• To investigate the impact of electronic polarization on protein structural stability during molecular dynamics (MD) simulations.
• To evaluate the efficacy of the MFCC-PB approach in generating accurate PPC for MD simulations.

Main Methods:

• Molecular dynamics (MD) simulations were performed on benchmark proteins.
• Two sets of atomic charges were used: standard AMBER and polarized protein-specific charge (PPC).
• PPC were derived using a molecular fractionation with conjugate caps-Poisson-Boltzmann (MFCC-PB) approach.

Main Results:

• Hydrogen bond occupancy and number were consistently higher with PPC than with AMBER charges.
• Some intra-protein hydrogen bonds, broken with AMBER charges, remained stable with PPC.
• AMBER charge simulations led to local structure deformation or denaturation due to hydrogen bond breaking.

Conclusions:

• Polarized protein-specific charges (PPC) significantly enhance the dynamic stability of intra-protein hydrogen bonds.
• Electronic polarization, as captured by PPC, plays a vital role in stabilizing protein structures during MD simulations.
• The MFCC-PB approach provides a reliable method for deriving PPC, improving the accuracy of MD simulations for protein dynamics.