Physicochemical stability study of protein-benzoic acid complexes using molecular dynamics simulations

Area of Science:

• Biochemistry
• Computational Chemistry
• Structural Biology

Background:

• Carboxyl-modified substrates are widely used to stabilize therapeutic proteins.
• Understanding protein-ligand interactions is vital for drug development and delivery systems.

Purpose of the Study:

• To investigate the stability and binding interactions of protein-benzoic acid complexes.
• To elucidate the structural dynamics of bovine serum albumin (BSA), zein, and lysozyme in complex with benzoic acid.

Main Methods:

• Homology modeling for zein structure generation.
• Molecular docking to create protein-benzoic acid complex models.
• Molecular dynamics simulations to assess complex stability.
• Analysis of Root-Mean-Square Deviation (RMSD), radius of gyration, and solvent accessible surface area.

Main Results:

• Protein-benzoic acid complexes exhibited significant stability and compactness.
• Two primary binding modes were identified, with one dominating (86-91% conformations).
• Hydrogen bonding, hydrophobic, and electrostatic interactions were key to binding.
• Lysozyme's binding cavity showed higher surface accessibility.
• Complexes with BSA and lysozyme were found to be more stable than with zein.

Conclusions:

• Benzoic acid forms stable complexes with BSA, zein, and lysozyme, supported by computational evidence.
• The study provides crucial insights into the dynamics and structural basis of these interactions.
• Findings are significant for enhancing the stability of therapeutic protein drugs utilizing carboxyl substrates.