Evaluation of the field-adapted ADMA approach: absolute and relative energies of crambin and derivatives

Abstract

A large number of conformations and chemically modified variants of the protein crambin were used to extensively test the field-adapted adjustable density matrix assembler (FA-ADMA) method developed for ab initio quality quantum chemistry computations of proteins and other macromolecules, introduced in an earlier publication. In this method, the fuzzy density matrix fragmentation scheme of the original adjustable density matrix assembler (ADMA) method has been made more efficient by combining it with an approach of using point charges to approximate the effects of additional, distant parts of a given macromolecule in the quantum chemical calculation of each fragment. In this way, smaller parent molecues can be used for fragment generation, while achieving accuracy that can be obtained only with large parent molecules in the original ADMA method. Whereas in both methods the error relative to the Hartree–Fock result can be reduced below any threshold by choosing large enough parent molecules, this can be done more efficiently with the new method. In order to obtain reliable test results for the accuracy obtainable by the new method when compared to conventional Hartree–Fock calculations, we performed a large number of energy calculations for the protein crambin using various conformations available in the Protein Data Bank, various protonation states, and side chain mutations. Additionally, in order to test the performance of the method for protein–solvent interaction studies, the energy changes due to the formation of complexes with ethanol and single and multiple water molecules were investigated.