Fully quantum mechanical energy optimization for protein-ligand structure

Yun Xiang, D. W. Zhang, John Z.H. Zhang

Research output: Contribution to journalArticlepeer-review


We present a quantum mechanical approach to study protein-ligand binding structure with application to a Adipocyte lipid-binding protein complexed with Propanoic Acid. The present approach employs a recently develop molecular fractionation with a conjugate caps (MFCC) method to compute protein-ligand interaction energy and performs energy optimization using the quasi-Newton method. The MFCC method enables us to compute fully quantum mechanical ab initio protein-ligand interaction energy and its gradients that are used in energy minimization. This quantum optimization approach is applied to study the Adipocyte lipid-binding protein complexed with Propanoic Acid system, a complex system consisting of a 2057-atom protein and a 10-atom ligand. The MFCC calculation is carried out at the Hartree-Fock level with a 3-21G basis set. The quantum optimized structure of this complex is in good agreement with the experimental crystal structure. The quantum energy calculation is implemented in a parallel program that dramatically speeds up the MFCC calculation for the protein-ligand system. Similarly good agreement between MFCC optimized structure and the experimental structure is also obtained for the streptavidin-biotin complex. Due to heavy computational cost, the quantum energy minimization is carried out in a six-dimensional space that corresponds to the rigid-body protein-ligand interaction.

Original languageEnglish (US)
Pages (from-to)1431-1437
Number of pages7
JournalJournal of Computational Chemistry
Issue number12
StatePublished - Sep 2004


  • Protein-ligand structure
  • Quantum mechanical energy optimization

ASJC Scopus subject areas

  • General Chemistry
  • Computational Mathematics


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