uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Scrutinizing Molecular Mechanics Force Fields on the Submicrosecond Timescale with NMR Data
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
2010 (English)In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 99, no 2, 647-655 p.Article in journal (Refereed) Published
Abstract [en]

Protein dynamics on the atomic level and on the microsecond timescale has recently become accessible from both computation and experiment. To validate molecular dynamics (MD) at the submicrosecond timescale against experiment we present microsecond MD simulations in 10 different force-field configurations for two globular proteins, ubiquitin and the gb3 domain of protein G, for which extensive NMR data is available. We find that the reproduction of the measured NMR data strongly depends on the chosen force field and electrostatics treatment. Generally, particle-mesh Ewald outperforms cut-off and reaction-field approaches. A comparison to measured J-couplings across hydrogen bonds suggests that there is room for improvement in the force-field description of hydrogen bonds in most modern force fields. Our results show that with current force fields, simulations beyond hundreds of nanoseconds run an increased risk of undergoing transitions to nonnative conformational states or will persist within states of high free energy for too long, thus skewing the obtained population frequencies. Only for the AMBER99sb force field have such transitions not been observed. Thus, our results have significance for the interpretation of data obtained with long MD simulations, for the selection of force fields for MD studies and for force-field development. We hope that this comprehensive benchmark based on NMR data applied to many popular MD force fields will serve as a useful resource to the MD community. Finally, we find that for gb3, the force-field AMBER99sb reaches comparable accuracy in back-calculated residual dipolar couplings and J-couplings across hydrogen bonds to ensembles obtained by refinement against NMR data.

Place, publisher, year, edition, pages
2010. Vol. 99, no 2, 647-655 p.
National Category
Biological Sciences
URN: urn:nbn:se:uu:diva-135960DOI: 10.1016/j.bpj.2010.04.062ISI: 000280182300039PubMedID: 20643085OAI: oai:DiVA.org:uu-135960DiVA: diva2:375905
Available from: 2010-12-09 Created: 2010-12-09 Last updated: 2010-12-09Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Department of Cell and Molecular Biology
In the same journal
Biophysical Journal
Biological Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 174 hits
ReferencesLink to record
Permanent link

Direct link