Revisiting Hydrogen Bond Thermodynamics in Molecular Simulations

Area of Science:

• Physical Chemistry
• Computational Chemistry
• Biophysics

Background:

• Hydrogen bonds are crucial in aqueous solutions and biomolecular interactions, influencing molecular stability, conformation, and interactions.
• Quantifying hydrogen bond strength is essential for understanding molecular behavior and mechanisms.

Purpose of the Study:

• To propose a simple and broadly applicable methodology for extracting hydrogen bond strength from atomistic simulations.
• To uniquely define the free energy, entropy, and enthalpy of hydrogen bonds.

Main Methods:

• Calculating the free energy of hydrogen bond formation as the reversible work to transform a random pair distribution to one with formed hydrogen bonds.
• Utilizing the probability density distribution of donor-acceptor pairs in the first solvation shell of an electronegative atom.

Main Results:

• The developed method accurately quantifies hydrogen bond free energy, entropy, and enthalpy.
• The methodology is demonstrated on water-water hydrogen bonds in pure water and trehalose-water mixtures using molecular dynamics simulations.

Conclusions:

• The proposed method offers a simple yet powerful approach to assess hydrogen bond strength in diverse molecular systems.
• This technique is valuable for investigating the role of hydrogen bonds in various molecular mechanisms and processes.