A Fragment Quantum Mechanical Method for Metalloproteins

Mingyuan Xu, Xiao He, Tong Zhu, John Z.H. Zhang

Research output: Contribution to journalArticlepeer-review


An accurate energy calculation of metalloprotein is of crucial importance and also a theoretical challenge. In this work, a metal molecular fractionation with conjugate caps (metal-MFCC) approach is developed for efficient linear-scaling quantum calculation of potential energy and atomic forces of metalloprotein. In this approach, the potential energy of a given protein is calculated by a linear combination of potential energies of the neighboring residues, two-body interaction energy between non-neighboring residues that are spatially in close contact and the potential energy of the metal binding group. The calculation of each fragment is embedded in a field of point charges representing the remaining protein environment. Numerical studies were carried out to check the performance of this method, and the calculated potential energies and atomic forces all show excellent agreement with the full system calculations at the M06-2X/6-31G(d) level. By combining the energy calculation with molecular dynamic simulation, we performed an ab initio structural optimization for a zinc finger protein with high efficiency. The present metal-MFCC approach is linear-scaling with a low prefactor and trivially parallelizable. The individual fragment typically contains about 50 atoms, and it is thus possible to be calculated at higher levels of the quantum chemistry method. This fragment method can be routinely applied to perform structural optimization and ab initio molecular dynamic simulation for metalloproteins of any size.

Original languageEnglish (US)
Pages (from-to)1430-1439
JournalJournal of chemical theory and computation
Issue number2
StatePublished - Feb 12 2019

ASJC Scopus subject areas

  • Computer Science Applications
  • Physical and Theoretical Chemistry


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