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Insight towards the conserved water mediated recognition of catalytic and structural Zn(+2) ions in human Matrix Metalloproteinase-8 enzyme: A study by MD-simulation methods.

Chakrabarti B, Bairagya HR, Mishra DK, Chatterjee PK, Mukhopadhyay BP - Bioinformation (2013)

Bottom Line: The coordination of two conserved water molecules (W and WS) to ZnS and the H-bonding interaction of WS to S151 have indicated the plausible involvement of that metal ion in the catalytic process.Beside this the coupling of ZnC and ZnS metal ions (ZnC - W(H) (W(1))…..W(2) ….H(162) - ZnS) through two conserved hydrophilic centers (occupied by water molecules) may also provide some rational on the recognition of two zinc ions which were separated by ~13 Å in their X-ray structures.This unique recognition of both the Zn(+2) ions in the enzyme through conserved water molecules may be implemented/ exploited for the design of antiproteolytic agent using water mimic drug design protocol.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, National Institute of Technology, Durgapur - 713 209, W.B. India.

ABSTRACT
Human matrix metalloproteinase-8 (hMMP-8) plays a important role in the progression of colorectal cancer, metastasis, multiple sclerosis and rheumetoid arthritis. Extensive MD-simulation of the PDB and solvated structures of hMMP-8 has revealed the presence of few conserved water molecules around the catalytic and structural zinc (ZnC and ZnS) ions. The coordination of two conserved water molecules (W and WS) to ZnS and the H-bonding interaction of WS to S151 have indicated the plausible involvement of that metal ion in the catalytic process. Beside this the coupling of ZnC and ZnS metal ions (ZnC - W(H) (W(1))…..W(2) ….H(162) - ZnS) through two conserved hydrophilic centers (occupied by water molecules) may also provide some rational on the recognition of two zinc ions which were separated by ~13 Å in their X-ray structures. This unique recognition of both the Zn(+2) ions in the enzyme through conserved water molecules may be implemented/ exploited for the design of antiproteolytic agent using water mimic drug design protocol.

No MeSH data available.


Related in: MedlinePlus

The binding free energy of Znc and Zns in 1 BZSstructure during 5ns MD Simulation.
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Related In: Results  -  Collection


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Figure 1: The binding free energy of Znc and Zns in 1 BZSstructure during 5ns MD Simulation.

Mentions: For investigating the role of water molecules, solvation ofnative PDB structures was done by creating a water box ofdimension 10 × 10 × 10 Å3, using solvate 1.2 plugin within theVisual Molecular Dynamics v. 1.8.6. program [19] and MDsimulations were followed. Total ~ 2196 water molecules (TIP3Pwater model) were used to immerse each molecule. Themolecular dynamics of each structure was performed byconverting the solvated and PDB structures to Protein StructureFile (PSF) using the tool Automatic PSF Generation Plugin–1.0 vby applying CHARMM force field [20,21] within the VisualMolecular Dynamics v. 1.8.6. All the ten (five PDB and theirsolvated) structures were simulated. All the structures wereinitially energy minimized (100 cycles to eliminate initialcontacts which would destabilize the system) using CHARMMforce field. After energy minimization all the structures weresimulated using Auto Interactive Molecular Dynamics (IMD)v.1.8.6 and Nanoscale Molecular Dynamics v.2.6. [22]. Duringsimulation, the whole system was allowed to move freely [23].The molecular simulations were followed upto 5 ns for eachstructure (where time step was 2fs) at 300K temperature bymeans of Langevin dynamics [24]. The whole system wasconverged within 500ps and the simulation was adequatelyconverged within 2ns (Figure 1). During the dynamics, severalsnapshots were recorded (every 2ps) to investigate the detailcoordination or interaction of water molecules with the Zinc(ZnC / ZnS) ions.


Insight towards the conserved water mediated recognition of catalytic and structural Zn(+2) ions in human Matrix Metalloproteinase-8 enzyme: A study by MD-simulation methods.

Chakrabarti B, Bairagya HR, Mishra DK, Chatterjee PK, Mukhopadhyay BP - Bioinformation (2013)

The binding free energy of Znc and Zns in 1 BZSstructure during 5ns MD Simulation.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3569599&req=5

Figure 1: The binding free energy of Znc and Zns in 1 BZSstructure during 5ns MD Simulation.
Mentions: For investigating the role of water molecules, solvation ofnative PDB structures was done by creating a water box ofdimension 10 × 10 × 10 Å3, using solvate 1.2 plugin within theVisual Molecular Dynamics v. 1.8.6. program [19] and MDsimulations were followed. Total ~ 2196 water molecules (TIP3Pwater model) were used to immerse each molecule. Themolecular dynamics of each structure was performed byconverting the solvated and PDB structures to Protein StructureFile (PSF) using the tool Automatic PSF Generation Plugin–1.0 vby applying CHARMM force field [20,21] within the VisualMolecular Dynamics v. 1.8.6. All the ten (five PDB and theirsolvated) structures were simulated. All the structures wereinitially energy minimized (100 cycles to eliminate initialcontacts which would destabilize the system) using CHARMMforce field. After energy minimization all the structures weresimulated using Auto Interactive Molecular Dynamics (IMD)v.1.8.6 and Nanoscale Molecular Dynamics v.2.6. [22]. Duringsimulation, the whole system was allowed to move freely [23].The molecular simulations were followed upto 5 ns for eachstructure (where time step was 2fs) at 300K temperature bymeans of Langevin dynamics [24]. The whole system wasconverged within 500ps and the simulation was adequatelyconverged within 2ns (Figure 1). During the dynamics, severalsnapshots were recorded (every 2ps) to investigate the detailcoordination or interaction of water molecules with the Zinc(ZnC / ZnS) ions.

Bottom Line: The coordination of two conserved water molecules (W and WS) to ZnS and the H-bonding interaction of WS to S151 have indicated the plausible involvement of that metal ion in the catalytic process.Beside this the coupling of ZnC and ZnS metal ions (ZnC - W(H) (W(1))…..W(2) ….H(162) - ZnS) through two conserved hydrophilic centers (occupied by water molecules) may also provide some rational on the recognition of two zinc ions which were separated by ~13 Å in their X-ray structures.This unique recognition of both the Zn(+2) ions in the enzyme through conserved water molecules may be implemented/ exploited for the design of antiproteolytic agent using water mimic drug design protocol.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, National Institute of Technology, Durgapur - 713 209, W.B. India.

ABSTRACT
Human matrix metalloproteinase-8 (hMMP-8) plays a important role in the progression of colorectal cancer, metastasis, multiple sclerosis and rheumetoid arthritis. Extensive MD-simulation of the PDB and solvated structures of hMMP-8 has revealed the presence of few conserved water molecules around the catalytic and structural zinc (ZnC and ZnS) ions. The coordination of two conserved water molecules (W and WS) to ZnS and the H-bonding interaction of WS to S151 have indicated the plausible involvement of that metal ion in the catalytic process. Beside this the coupling of ZnC and ZnS metal ions (ZnC - W(H) (W(1))…..W(2) ….H(162) - ZnS) through two conserved hydrophilic centers (occupied by water molecules) may also provide some rational on the recognition of two zinc ions which were separated by ~13 Å in their X-ray structures. This unique recognition of both the Zn(+2) ions in the enzyme through conserved water molecules may be implemented/ exploited for the design of antiproteolytic agent using water mimic drug design protocol.

No MeSH data available.


Related in: MedlinePlus