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This article is part of the supplement: BioSysBio 2007: Systems Biology, Bioinformatics, Synthetic Biology

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Design of novel semisynethetic metalloenzyme from thermolysin

Mohd Basyaruddin Abdul Rahman1*, Ahmad Haniff Jaafar1, Mahiran Basri1, Raja Noor Zaliha Raja Abdul Rahman2, Abu Bakar Salleh2 and Habibah Abdul Wahab3

Author Affiliations

1 Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

2 Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

3 Laborotary of Biocrystallography and Bioinformatic Structure, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia

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BMC Systems Biology 2007, 1(Suppl 1):P68  doi:10.1186/1752-0509-1-S1-P68

The electronic version of this article is the complete one and can be found online at:

Published:8 May 2007

© 2007 Rahman et al; licensee BioMed Central Ltd.


Initial applications of biocatalysis involved the used of naturally occurring enzyme. With new challenges in green chemical reaction, biocatalyst that shed the light is metalloenzyme, which function as enzyme and contain metal that are tightly attached and always isolated with the protein [1]. In recent years, enzyme engineering has proven to be an invaluable tool for elucidating biocatalytic mechanisms as well as producing enzymes for industrial purposes. Approaches developed for in vivo chemical modification and in silico computational methods promise to increase the scope and have already been used successfully to alter existing protein so that they have better stability and functionality [2]. This task might be good to address in designing a new biocatalyst with improved properties.


The AutoDock programme 3.05 was employed in order to identify the binding conformations of the ligands and the metal ions and to perform docking using Lamarckian Genetic Algorithm (LGA) [3]. The coordinate of thermolysin-substrate free structure coded as 1KEI was taken from Brookhaven Protein Data Bank (PDB).


The predicted KEI-ligand complexes with the lowest final docked energy for PSE and PHN were -6.71 kcal/mol at pocket 45 and -6.60 kcal/mol at pocket 47, respectively. Non-covalent interactions of hydrogen bond and hydrophobic interaction between protein and ligands established the final conformation. Analysis on finding the most favorable metal ions to dock onto each complex found that Mg2+ was docked onto KEI-PSE45 complex with final docked energy of -1.09 kcal/mol and performed four interactions with the PSE ligand. Meanwhile, Ca2+ represented the best metal ions to dock to the KEI-PHN47 complex with final docked energy of -4.12 kcal/mol and performed three interactions with the nearby residues.


An important branch of novel protein design is through engineering and design of new metal-binding sites into native proteins. By employing in silico approach of molecular docking, screening of putative ligand for possible interactions may enhance the discovery of novel semisynthetic enzyme and lead to a new protein function. Finally, the framework which was introduced for the experiment may be a competent method for screening potential metal ions in this in vivo route.


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