Abstract
Understanding the protein adsorption onto solid surface is of critical importance in the field of bioengineering, such as medical implants, diagnostic biosensors, drug delivery systems, and tissue engineering. This study proposed molecular dynamics (MD) simulations to investigate the physical mechanism of cobra cardiotoxin (CTX) proteins adsorption on alkanethiol self-assembled monolayers (SAMs) composed of S(CH2)5CH3 and S(CH2)9CH3. The binding energy of the CTX protein to the SAM surface of different mixing ratios of alkanethiol chains was calculated. The physical mechanisms are examined to understand how these parameters affect the adsorption of a CTX protein on SAM surfaces. Dynamic information, such as force, structural change, interaction energy, and potential of mean force (PMF), about the desorption of a single CTX protein from SAM surface was investigated by means of steered molecular dynamics (SMD) simulations. By applying Jarzynski’s equality, the PMF can be reconstructed from the SMD simulation. The PMFs, calculated by different estimators based upon Jarzynski’s equality, were compared with the conventional umbrella sampling method. The free energies of a CTX protein adsorption onto SAMs with different mixing ratios were investigated. Enhancement of the adsorption affinity, i.e., the change in free energy of adsorption, for mixed SAMs was determined. A component analysis conducted to quantify the physical mechanisms that promoted CTX adsorption revealed contributions from both SAMs and the solvent. Further component analyses of thermodynamic properties, such as the free energy, enthalpy, and entropy, indicated that the contribution from SAMs was driven by enthalpy, and the contribution from the solvent was driven by entropy.