Limits...
Predicting protein interactions by Brownian dynamics simulations.

Meng XY, Xu Y, Zhang HX, Mezei M, Cui M - J. Biomed. Biotechnol. (2012)

Bottom Line: In order to reduce the computational costs for energy evaluations, a shell-based grid force field was developed to represent the receptor protein and solvation effects.Furthermore, we have developed an approach to account for the flexibility of proteins, which has been successfully applied to reproduce the experimental complex structure from the structure of two unbounded proteins.These results indicate that this adapted BD protein docking approach can be useful for the prediction of protein-protein interactions.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA 23298, USA.

ABSTRACT
We present a newly adapted Brownian-Dynamics (BD)-based protein docking method for predicting native protein complexes. The approach includes global BD conformational sampling, compact complex selection, and local energy minimization. In order to reduce the computational costs for energy evaluations, a shell-based grid force field was developed to represent the receptor protein and solvation effects. The performance of this BD protein docking approach has been evaluated on a test set of 24 crystal protein complexes. Reproduction of experimental structures in the test set indicates the adequate conformational sampling and accurate scoring of this BD protein docking approach. Furthermore, we have developed an approach to account for the flexibility of proteins, which has been successfully applied to reproduce the experimental complex structure from the structure of two unbounded proteins. These results indicate that this adapted BD protein docking approach can be useful for the prediction of protein-protein interactions.

Show MeSH
A schematic representation of the Brownian dynamics simulations of the association between two proteins. Simulations are conducted in coordinates defined relative to the position of the center of the protein, protein I.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3303761&req=5

fig1: A schematic representation of the Brownian dynamics simulations of the association between two proteins. Simulations are conducted in coordinates defined relative to the position of the center of the protein, protein I.

Mentions: For the BD simulations of protein-protein interactions, there are only two solute particles, the receptor and ligand proteins treated as rigid bodies. In this study, the receptor of the complex was defined as protein I and was kept fixed with its center of mass (COM) at the origin while the ligand was defined as protein II of which translational and rotational motions were simulated (Figure 1). In each trajectory, protein II starts with a random orientation and position on the b-surface, which was defined as the sum of the maximum radii of the two proteins plus 2 Å. Protein II was subjected to three forces: electrostatic, the random Brownian force, and the frictional force due to solvent viscosity. During the simulation, the motion of the complex(es) satisfying the reaction criteria for encounter complex formation is retained as an effective trajectory [30]. Within such an effective trajectory, two configurations which have lowest electrostatics interaction energy and shortest distance between protein I and protein II, respectively, are recorded as two independent sampled conformations. The trajectory was terminated when protein II either escaped out of the c-surface (5 Å outside of the b surface) or was running longer than 20 ns.


Predicting protein interactions by Brownian dynamics simulations.

Meng XY, Xu Y, Zhang HX, Mezei M, Cui M - J. Biomed. Biotechnol. (2012)

A schematic representation of the Brownian dynamics simulations of the association between two proteins. Simulations are conducted in coordinates defined relative to the position of the center of the protein, protein I.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3303761&req=5

fig1: A schematic representation of the Brownian dynamics simulations of the association between two proteins. Simulations are conducted in coordinates defined relative to the position of the center of the protein, protein I.
Mentions: For the BD simulations of protein-protein interactions, there are only two solute particles, the receptor and ligand proteins treated as rigid bodies. In this study, the receptor of the complex was defined as protein I and was kept fixed with its center of mass (COM) at the origin while the ligand was defined as protein II of which translational and rotational motions were simulated (Figure 1). In each trajectory, protein II starts with a random orientation and position on the b-surface, which was defined as the sum of the maximum radii of the two proteins plus 2 Å. Protein II was subjected to three forces: electrostatic, the random Brownian force, and the frictional force due to solvent viscosity. During the simulation, the motion of the complex(es) satisfying the reaction criteria for encounter complex formation is retained as an effective trajectory [30]. Within such an effective trajectory, two configurations which have lowest electrostatics interaction energy and shortest distance between protein I and protein II, respectively, are recorded as two independent sampled conformations. The trajectory was terminated when protein II either escaped out of the c-surface (5 Å outside of the b surface) or was running longer than 20 ns.

Bottom Line: In order to reduce the computational costs for energy evaluations, a shell-based grid force field was developed to represent the receptor protein and solvation effects.Furthermore, we have developed an approach to account for the flexibility of proteins, which has been successfully applied to reproduce the experimental complex structure from the structure of two unbounded proteins.These results indicate that this adapted BD protein docking approach can be useful for the prediction of protein-protein interactions.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA 23298, USA.

ABSTRACT
We present a newly adapted Brownian-Dynamics (BD)-based protein docking method for predicting native protein complexes. The approach includes global BD conformational sampling, compact complex selection, and local energy minimization. In order to reduce the computational costs for energy evaluations, a shell-based grid force field was developed to represent the receptor protein and solvation effects. The performance of this BD protein docking approach has been evaluated on a test set of 24 crystal protein complexes. Reproduction of experimental structures in the test set indicates the adequate conformational sampling and accurate scoring of this BD protein docking approach. Furthermore, we have developed an approach to account for the flexibility of proteins, which has been successfully applied to reproduce the experimental complex structure from the structure of two unbounded proteins. These results indicate that this adapted BD protein docking approach can be useful for the prediction of protein-protein interactions.

Show MeSH