Complexation Mechanisms of Aqueous Amylose: Molecular Dynamics Study Using 3-Pentadecylphenol

Area of Science:

• Supramolecular Chemistry
• Computational Chemistry
• Biophysics

Background:

• Amylose, a polysaccharide, can form inclusion complexes with various small molecules.
• 3-pentadecylphenol (PDP) is a natural product with surfactant properties, suggesting potential interactions with amylose.
• Understanding guest-host complexation in aqueous solution is crucial for applications in drug delivery and material science.

Purpose of the Study:

• To investigate the molecular mechanisms of 3-pentadecylphenol (PDP) complexation with linear amylose fragments in aqueous solution using molecular dynamics (MD) simulations.
• To characterize the influence of temperature and PDP concentration on the binding modes and stability of amylose-PDP complexes.
• To quantify the thermodynamic parameters of inclusion and nonspecific complexation.

Main Methods:

• Molecular dynamics (MD) simulations of amylose fragments (10-40 glucose units) complexed with 3-pentadecylphenol (PDP) in aqueous solution across a temperature range (277-433 K).
• Cluster analysis (CA) for preliminary trajectory analysis.
• Solvent Accessible Surface Area (SASA) determination, corrected for intrinsic conformational changes of PDP, combined with a hidden Markov model (HMM) for quantitative aggregate analysis.

Main Results:

• Amylose-PDP binding is primarily governed by hydrophobic interactions and excluded volume effects.
• Stable complexes exhibit guest-host inclusion, with PDP residing within the amylose helical structure.
• At elevated temperatures, nonspecific interactions become more prevalent than inclusion complexation.
• Excess PDP leads to self-aggregation, preventing effective inclusion complexation.
• The enthalpy change for inclusion complexation (K_gh) was estimated at -75 kJ/mol, significantly higher than expected for solid-state complexes.
• Nonspecific binding (K_ns) exhibited an enthalpy change approximately half that of inclusion complexation.

Conclusions:

• Molecular dynamics simulations provide detailed insights into the temperature-dependent complexation behavior of amylose and PDP in water.
• The study highlights the distinct binding modes (inclusion vs. nonspecific) and their thermodynamic contributions.
• Findings suggest that optimal conditions for amylose-PDP inclusion complexation involve controlled PDP concentrations and moderate temperatures to avoid self-aggregation and favor specific interactions.