Starting Structure Dependence of NMR Order Parameters Derived from MD Simulations: Implications for Judging Force-field Quality

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 2008 Apr 29

PMID 18441027

Citations 9

Authors

Alrun N Koller

Harald Schwalbe

Holger Gohlke

Affiliations

Soon will be listed here.

Abstract

Comparing experimental generalized N-H S(2) order parameters to those calculated from molecular dynamics trajectories is increasingly used to judge force-field quality and completeness of sampling. Herein we demonstrate for the well-investigated system hen egg white lysozyme that different experimental starting structures can lead to significant differences in molecular-dynamics-derived S(2) parameters that can be even larger than S(2) parameter deviations due to different force fields. Caution should thus be taken in general when simulated S(2) parameters are compared to experimental data with the aim of judging force-field quality. We show that adequately sampling flexible regions ( approximately 100 ns) and only calculating S(2) parameters averaged over short time windows proved necessary to obtain consistent results irrespective of the starting structure.

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References

Case D, Cheatham 3rd T, Darden T, Gohlke H, Luo R, Merz Jr K . The Amber biomolecular simulation programs. J Comput Chem. 2005; 26(16):1668-88. PMC: 1989667. DOI: 10.1002/jcc.20290. View

Buck M, Bouguet-Bonnet S, Pastor R, MacKerell Jr A . Importance of the CMAP correction to the CHARMM22 protein force field: dynamics of hen lysozyme. Biophys J. 2005; 90(4):L36-8. PMC: 1367299. DOI: 10.1529/biophysj.105.078154. View

Horita D, Zhang W, Smithgall T, Gmeiner W, Byrd R . Dynamics of the Hck-SH3 domain: comparison of experiment with multiple molecular dynamics simulations. Protein Sci. 2000; 9(1):95-103. PMC: 2144440. DOI: 10.1110/ps.9.1.95. View

Soares T, Daura X, Oostenbrink C, Smith L, van Gunsteren W . Validation of the GROMOS force-field parameter set 45Alpha3 against nuclear magnetic resonance data of hen egg lysozyme. J Biomol NMR. 2005; 30(4):407-22. DOI: 10.1007/s10858-004-5430-1. View

Prompers J, Bruschweiler R . General framework for studying the dynamics of folded and nonfolded proteins by NMR relaxation spectroscopy and MD simulation. J Am Chem Soc. 2002; 124(16):4522-34. DOI: 10.1021/ja012750u. View

Showalter S, Bruschweiler R . Validation of Molecular Dynamics Simulations of Biomolecules Using NMR Spin Relaxation as Benchmarks: Application to the AMBER99SB Force Field. J Chem Theory Comput. 2015; 3(3):961-75. DOI: 10.1021/ct7000045. View

Hornak V, Abel R, Okur A, Strockbine B, Roitberg A, Simmerling C . Comparison of multiple Amber force fields and development of improved protein backbone parameters. Proteins. 2006; 65(3):712-25. PMC: 4805110. DOI: 10.1002/prot.21123. View

Smith L, Mark A, Dobson C, van Gunsteren W . Comparison of MD simulations and NMR experiments for hen lysozyme. Analysis of local fluctuations, cooperative motions, and global changes. Biochemistry. 1995; 34(34):10918-31. DOI: 10.1021/bi00034a026. View

Bruschweiler R . New approaches to the dynamic interpretation and prediction of NMR relaxation data from proteins. Curr Opin Struct Biol. 2003; 13(2):175-83. DOI: 10.1016/s0959-440x(03)00036-8. View

10.

Nederveen A, Bonvin A . NMR Relaxation and Internal Dynamics of Ubiquitin from a 0.2 μs MD Simulation. J Chem Theory Comput. 2015; 1(3):363-74. DOI: 10.1021/ct0498829. View

11.

Stocker U, van Gunsteren W . Molecular dynamics simulation of hen egg white lysozyme: a test of the GROMOS96 force field against nuclear magnetic resonance data. Proteins. 2000; 40(1):145-53. View

12.

Schwalbe H, Grimshaw S, Spencer A, Buck M, Boyd J, Dobson C . A refined solution structure of hen lysozyme determined using residual dipolar coupling data. Protein Sci. 2001; 10(4):677-88. PMC: 2373969. DOI: 10.1110/ps.43301. View

13.

Halle B . Flexibility and packing in proteins. Proc Natl Acad Sci U S A. 2002; 99(3):1274-9. PMC: 122180. DOI: 10.1073/pnas.032522499. View

14.

Case D . Molecular dynamics and NMR spin relaxation in proteins. Acc Chem Res. 2002; 35(6):325-31. DOI: 10.1021/ar010020l. View

15.

Buck M, Boyd J, Redfield C, Mackenzie D, Jeenes D, Archer D . Structural determinants of protein dynamics: analysis of 15N NMR relaxation measurements for main-chain and side-chain nuclei of hen egg white lysozyme. Biochemistry. 1995; 34(12):4041-55. DOI: 10.1021/bi00012a023. View

16.

Andrews B, Romo T, Clarage J, Pettitt B, Phillips Jr G . Characterizing global substates of myoglobin. Structure. 1998; 6(5):587-94. DOI: 10.1016/s0969-2126(98)00060-4. View