Active site modeling in copper azurin molecular dynamics simulations.

Bruno Rizzuti¹, Marcel Swart, Luigi Sportelli

¹Dipartimento di Fisica and Unità INFM, Laboratorio di Biofisica Molecolare, Università della Calabria, Ponte P. Bucci, Cubo 30C, 87030 Rende CS, Italy.

|December 24, 2003

Summary

Active site modeling in copper azurin (CuA) simulations shows that constraints, not charge variations, maintain active site geometry. Met121 coordination is flexible, with distinct Cu-N bonds to His residues.

Area of Science:

Biophysical Chemistry
Computational Biology
Protein Dynamics

Background:

Accurate modeling of metalloprotein active sites is crucial for understanding their function.
Molecular dynamics (MD) simulations require precise representation of metal-ligand interactions.
Copper azurin (CuA) serves as a model system for studying electron transfer proteins.

Purpose of the Study:

To investigate the impact of electrostatic and constrained modeling on the copper active site in CuA MD simulations.
To evaluate the sensitivity of active site geometry to charge modifications and distance constraints.
To determine optimal modeling strategies for CuA simulations under unfolding conditions.

Main Methods:

Performed five 5 ns molecular dynamics simulations of reduced copper azurin at room temperature.
Employed mixed electrostatic and constrained modeling for copper-ligand coordination.
Varied charge states for ligand residues and tested distance constraints on coordinating atoms.

Main Results:

Active site geometry remained largely unaffected by charge variations when all five ligand atoms had distance constraints.
Removing the distance constraint on the oxygen atom of Gly45 did not alter active site geometry.
The coordination of copper to the axial ligand Methionine 121 (Met121) was found to be flexible.
Asymmetric coordination was observed between the copper ion and the nitrogen atoms of Histidine 46 (His46) and Histidine 117 (His117).

Conclusions:

Distance constraints are more critical than charge modifications for maintaining CuA active site geometry in MD simulations.
The flexibility of Met121 coordination and asymmetry in Cu-N bonds highlight specific dynamic features.
These findings inform the development of robust CuA models for simulating protein unfolding.

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Active site modeling in copper azurin molecular dynamics simulations.

Area of Science:

Background:

Purpose of the Study:

Main Methods:

Main Results:

Conclusions:

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