Simultaneous Use Of Class-i And Class-ii Force Fields In CHARMM For Solid-liquid Multiphase Simulation Of Protein-surface Interaction

Abstract

An appropriate understanding of conformational and behavioral changes of proteins upon their adsorption to synthetic surfaces is of crucial importance in the development of biomaterials because the changes play a governing role in determining cellular responses to implanted materials and substrates for tissue engineering. A detailed analysis of molecular behavior is key to such an understanding, and classical molecular dynamic (MD) simulation is one of the direct methods of addressing this issue. However, one of the challenges in using MD simulation is that class-I force fields (CHARMM, AMBER, OPLS, etc.) that have been parameterized for proteins are not suitable for polymers (i.e., polymer crystal structure not maintained during simulation) and extensive class-II force fields (CFF, PCFF, COMPASS, etc.) have not been parameterized for use in proteins. We have extended the CHARMM code so as to use a dedicated class-I force field for the protein, a class-II force field (image bond extended CFF, or newly implemented PCFF) for the polymer surfaces, and tuned electrostatic and van der Waals parameters for the interphase interaction. Results will be presented on the insufficiency of class-I force field for polymers and the suitability of the use of dual (one class-I and one class-II) force fields for solid-liquid interphase interactions relevant for protein adsorption on PLA polymers.