Appadurai, R and Nagesh, J and Srivastava, A (2021) High resolution ensemble description of metamorphic and intrinsically disordered proteins using an efficient hybrid parallel tempering scheme. In: Nature Communications, 12 (1).
|
PDF
nat_com_12-01_2021.pdf - Published Version Download (3MB) | Preview |
|
|
PDF
41467_2021_21105_MOESM1_ESM.pdf - Published Supplemental Material Download (6MB) | Preview |
|
|
PDF
41467_2021_21105_MOESM2_ESM.pdf - Published Supplemental Material Download (4MB) | Preview |
|
|
PDF
41467_2021_21105_MOESM3_ESM.pdf - Published Supplemental Material Download (1MB) | Preview |
Abstract
Mapping free energy landscapes of complex multi-funneled metamorphic proteins and weakly-funneled intrinsically disordered proteins (IDPs) remains challenging. While rare-event sampling molecular dynamics simulations can be useful, they often need to either impose restraints or reweigh the generated data to match experiments. Here, we present a parallel-tempering method that takes advantage of accelerated water dynamics and allows efficient and accurate conformational sampling across a wide variety of proteins. We demonstrate the improved sampling efficiency by benchmarking against standard model systems such as alanine di-peptide, TRP-cage and β-hairpin. The method successfully scales to large metamorphic proteins such as RFA-H and to highly disordered IDPs such as Histatin-5. Across the diverse proteins, the calculated ensemble averages match well with the NMR, SAXS and other biophysical experiments without the need to reweigh. By allowing accurate sampling across different landscapes, the method opens doors for sampling free energy landscape of complex uncharted proteins. © 2021, The Author(s).
| Item Type: | Journal Article |
|---|---|
| Publication: | Nature Communications |
| Publisher: | Nature Research |
| Additional Information: | The copyright of this article belongs to Nature Research |
| Department/Centre: | Division of Biological Sciences > Molecular Biophysics Unit Division of Chemical Sciences > Solid State & Structural Chemistry Unit |
| Date Deposited: | 12 Mar 2021 16:06 |
| Last Modified: | 12 Mar 2021 16:06 |
| URI: | http://eprints.iisc.ac.in/id/eprint/68167 |
Actions (login required)
 |
View Item |
