English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Optimized molecular dynamics force fields applied to the helix-coil transition of polypeptides

MPS-Authors
There are no MPG-Authors available
External Ressource
No external resources are shared
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Best, R. B., & Hummer, G. (2009). Optimized molecular dynamics force fields applied to the helix-coil transition of polypeptides. The Journal of Physical Chemistry B, 113(26), 9004-9015. doi:10.1021/jp901540t.


Cite as: http://hdl.handle.net/21.11116/0000-0007-4AF9-E
Abstract
Obtaining the correct balance of secondary structure propensities is a central priority in protein force-field development. Given that current force fields differ significantly in their alpha-helical propensities, a correction to match experimental results would be highly desirable. We have determined simple backbone energy corrections for two force fields to reproduce the fraction of helix measured in short peptides at 300 K. As validation, we show that the optimized force fields produce results in excellent agreement with nuclear magnetic resonance experiments for folded proteins and short peptides not used in the optimization. However, despite the agreement at ambient conditions, the dependence of the helix content on temperature is too weak, a problem shared with other force fields. A fit of the Lifson-Roig helix-coil theory shows that both the enthalpy and entropy of helix formation are too small: the helix extension parameter w agrees well with experiment, but its entropic and enthalpic components are both only about half the respective experimental estimates. Our structural and thermodynamic analyses point toward the physical origins of these shortcomings in current force fields, and suggest ways to address them in future force-field development.