Gaseous bradykinin and its singly, doubly, and triply protonated forms: a first-principles study

Area of Science:

• Computational chemistry
• Molecular modeling
• Biophysics

Background:

• Bradykinin (BK) is a peptide hormone involved in various physiological processes.
• Understanding the conformational dynamics of BK and its protonated states is crucial for elucidating its function.
• Previous studies have explored BK's properties, but detailed theoretical investigations of its conformers in gaseous and protonated states are needed.

Purpose of the Study:

• To theoretically investigate the conformational properties of gaseous bradykinin (BK) and its protonated forms ([BK + H](+), [BK + 2H](2+), [BK + 3H](3+)).
• To compare theoretical findings with existing experimental data for validation.

Main Methods:

• Utilized a combination of Merck molecular force field, Hartree-Fock, and density functional theory for theoretical calculations.
• Analyzed the structures and stability of neutral and protonated bradykinin conformers.
• Calculated gas-phase basicity and population-weighted collision cross-sections.

Main Results:

• Neutral BK, [BK + H](+), and [BK + 2H](2+) exhibit compact, zwitterionic structures stabilized by internal solvation.
• [BK + 3H](3+) presents an elongated form due to the absence of a salt bridge.
• A conserved beta-turn structure was identified in the Ser(6)-Pro(7)-Phe(8)-Arg(9) sequence across all examined species.
• Calculated gas-phase basicity and collision cross-sections align well with experimental data.

Conclusions:

• The study provides detailed theoretical insights into the conformational landscape of bradykinin and its protonated states.
• The findings support experimental observations and enhance the understanding of bradykinin's structural behavior in the gas phase.
• Theoretical models accurately predict key properties of bradykinin conformers, aiding future research.