MFCC‐Based Fragmentation Methods for Biomolecules

Abstract

This chapter describes the molecular fractionation with conjugate caps (MFCC)-based fragmentation methods and their applications to biological systems. To account for the environmental polarization effect for each fragment calculation, electrostatic embedding was introduced into the GMFCC/molecular mechanics (MM) method which became the latest electrostatically embedded generalized molecular fractionation with conjugate caps (EE-GMFCC) method for more accurate calculation of the protein energy. The EE-GMFCC method is computationally efficient and linear-scaling with a low prefactor, and has been successfully applied to protein geometry optimization, molecular dynamics simulation, protein-ligand binding affinity calculation, and protein vibrational spectrum calculation at QM levels. The chapter combines the more accurate EE-GMFCC method with the CPCM model, denoted as EE-GMFCC-CPCM, for accurate calculation of protein solvation energy. To reduce the computational cost, the mechanical embedded (ME)-quantum mechanical (QM)/MM approach is used to describe the protein dynamics in explicit solvent while the water molecules are described by mechanical mechanics.