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Protein structure refinement of CASP target proteins using GNEIMO torsional dynamics method
Adrien B Larsen1, Jeffrey R Wagner, Abhinandan Jain
1Division of Immunology, Beckman Research Institute of the City of Hope , 1500, E. Duarte Road, Duarte, California 91010, United States.
Journal of Chemical Information and Modeling
|January 9, 2014
Summary
Computational protein structure prediction is improved using the GNEIMO method. This internal coordinate molecular dynamics (MD) technique refines low-resolution models into accurate atomistic structures without experimental data.
Area of Science:
- Computational Biology
- Structural Biology
- Biophysics
Background:
- Protein structure prediction remains a challenge, particularly refining low-resolution models into accurate atomistic representations for detailed studies.
- Internal coordinate molecular dynamics (MD) offers a potential solution by simplifying the physical model.
- The generalized Newton-Euler inverse mass operator (GNEIMO) technique has shown promise for refining small protein structures.
Purpose of the Study:
- To evaluate the efficacy of the GNEIMO technique with temperature replica exchange for refining low-resolution protein models.
- To assess the refinement capabilities of GNEIMO across a diverse set of protein targets.
- To compare GNEIMO's performance against traditional all-atom Cartesian MD methods.
Main Methods:
- Application of GNEIMO, an internal coordinate MD method, to refine low-resolution models of 30 proteins from the CASP competition.
- Utilizing temperature replica exchange to enhance conformational sampling during GNEIMO simulations.
- Modeling proteins as rigid clusters connected by torsional hinges, freezing high-frequency degrees of freedom.
Main Results:
- GNEIMO successfully refined low-resolution protein models, achieving up to 1.3 Å improvement in root-mean-square deviation (RMSD) for 30 CASP targets.
- Refinement was accomplished without the need for experimental data restraints.
- Unconstrained all-atom Cartesian MD simulations under identical conditions required restraints for comparable refinement.
Conclusions:
- The GNEIMO torsional MD method provides a robust and effective approach for refining low-resolution protein structures.
- This technique offers significant advantages over traditional Cartesian MD by enabling larger time steps and focusing conformational searches.
- GNEIMO represents a valuable tool for advancing computational protein structure prediction and detailed structural analysis.
