Thermodynamic investigations using molecular dynamics simulations with potential of mean force calculations for...

Understanding protein adsorption onto solid surfaces is of critical importance in the field of bioengineering, especially for applications such as medical implants, diagnostic biosensors, drug delivery systems, and tissue engineering. This study proposed the use of molecular dynamics simulations with potential of mean force (PMF) calculations to identify and characterize the mechanisms of adsorption of a protein molecule on a designed surface. A set of model systems consisting of a cardiotoxin (CTX) protein and mixed self-assembled monolayer (SAM) surfaces were used as examples. The set of mixed SAM surfaces with varying topographies were created by mixing alkanethiol chains of different lengths. The results revealed that CTX proteins underwent similar conformal changes upon adsorption onto the various mixed SAMs but showed distinctive characteristics in free energy profiles. Enhancement of the adsorption affinity, i.e., the change in free energy of adsorption, for mixed SAMs was demonstrated by using atomic force microscopic measurements. 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. The results indicated that CTX adsorption was an entropy-driven process, and the entropic component from the solvent, i.e., the hydrophobic interaction, was the major driving force for CTX adsorption onto SAMs. The study also concluded that the surfaces composed of mixtures of SAMs with different chain lengths promoted the adsorption of CTX protein.