A comparative study of various computational approaches in calculating the Structure of pyridoxal 5′-phosphate (PLP)-dependent β-lyase protein. the importance of protein environment

Rajeev Prabhakar, Keiji Morokuma, Djamaladdin G. Musaev

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Various computational approaches, using molecular mechanics (Amber), semiempirical (AMI), density functional (B3LYP), and various ONIOM methods, have been comparatively investigated for the structure of Escherichia coli NifS CsdB protein. The structure of the entire monomer containing 407 amino acid residues and 579 surrounding water molecules has been optimized. The full geometry optimization in the "active site-only" approach (including only active site atoms) has been found to give the largest root-mean-square (RMS) deviation from the X-ray structure; a much better agreement has been achieved by keeping the atoms leading to the backbones of some amino acids frozen in their positions in the X-ray structure. The best agreement has been attained by including the surrounding protein in the calculations using the two-layer ONIOM (B3LYP:Amber) approach. The results presented in this study conclusively demonstrate the importance of the protein/active-site interaction on the active-site structure of the enzyme. The present theoretical study represents the largest system studied at the ONIOM level to date, containing 7992 atoms, including 84 atoms in the QM region and rest in the MM region.

Original languageEnglish
Pages (from-to)443-446
Number of pages4
JournalJournal of Computational Chemistry
Volume26
Issue number5
DOIs
StatePublished - Apr 15 2005
Externally publishedYes

Fingerprint

Lyases
Pyridoxal Phosphate
Phosphate
Comparative Study
Phosphates
Amber
Proteins
Protein
Atoms
Dependent
Amino acids
Amino Acids
X rays
Molecular mechanics
Root mean square deviation
Molecular Mechanics
Escherichia coli
Backbone
Density Functional
Enzymes

Keywords

  • Active-site modeling
  • Enzyme modeling
  • ONIOM approach
  • Protein/active-site interaction
  • Pyridoxal 5′-phosphate (PLP)dependent protein

ASJC Scopus subject areas

  • Chemistry(all)
  • Safety, Risk, Reliability and Quality

Cite this

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abstract = "Various computational approaches, using molecular mechanics (Amber), semiempirical (AMI), density functional (B3LYP), and various ONIOM methods, have been comparatively investigated for the structure of Escherichia coli NifS CsdB protein. The structure of the entire monomer containing 407 amino acid residues and 579 surrounding water molecules has been optimized. The full geometry optimization in the {"}active site-only{"} approach (including only active site atoms) has been found to give the largest root-mean-square (RMS) deviation from the X-ray structure; a much better agreement has been achieved by keeping the atoms leading to the backbones of some amino acids frozen in their positions in the X-ray structure. The best agreement has been attained by including the surrounding protein in the calculations using the two-layer ONIOM (B3LYP:Amber) approach. The results presented in this study conclusively demonstrate the importance of the protein/active-site interaction on the active-site structure of the enzyme. The present theoretical study represents the largest system studied at the ONIOM level to date, containing 7992 atoms, including 84 atoms in the QM region and rest in the MM region.",
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