Modeling zinc in biomolecules with the self consistent charge-density functional tight binding (SCC-DFTB) method: applications to structural and energetic analysis

J Comput Chem. 2003 Apr 15;24(5):565-81. doi: 10.1002/jcc.10201.

Abstract

Parameters for the zinc ion have been developed in the self-consistent charge density functional tight-binding (SCC-DFTB) framework. The approach was tested against B3LYP calculations for a range of systems, including small molecules that contain the typical coordination environment of zinc in biological systems (cysteine, histidine, glutamic/aspartic acids, and water) and active site models for a number of enzymes such as alcohol dehydrogenase, carbonic anhydrase, and aminopeptidase. The SCC-DFTB approach reproduces structural and energetic properties rather reliably (e.g., total and relative ligand binding energies and deprotonation energies of ligands and barriers for zinc-assisted proton transfers), as compared with B3LYP/6-311+G** or MP2/6-311+G** calculations.

MeSH terms

  • Alcohol Dehydrogenase / chemistry*
  • Alcohol Dehydrogenase / metabolism
  • Algorithms*
  • Aminopeptidases / chemistry*
  • Aminopeptidases / metabolism
  • Aspartic Acid / chemistry
  • Aspartic Acid / metabolism
  • Bacterial Proteins*
  • Binding Sites
  • Carbonic Anhydrases / chemistry
  • Carbonic Anhydrases / metabolism
  • Cysteine / chemistry
  • Cysteine / metabolism
  • Glutamic Acid / chemistry
  • Glutamic Acid / metabolism
  • Histidine / chemistry
  • Histidine / metabolism
  • Liver / enzymology
  • Models, Molecular*
  • Molecular Conformation
  • Protein Binding
  • Protein Conformation*
  • Water / chemistry
  • Zinc* / chemistry
  • Zinc* / metabolism

Substances

  • Bacterial Proteins
  • Water
  • Aspartic Acid
  • Glutamic Acid
  • Histidine
  • Alcohol Dehydrogenase
  • Aminopeptidases
  • bacterial leucyl aminopeptidase
  • Carbonic Anhydrases
  • Zinc
  • Cysteine