Unknown

Dataset Information

0

Association of Peripheral Membrane Proteins with Membranes: Free Energy of Binding of GRP1 PH Domain with Phosphatidylinositol Phosphate-Containing Model Bilayers.


ABSTRACT: Understanding the energetics of peripheral protein-membrane interactions is important to many areas of biophysical chemistry and cell biology. Estimating free-energy landscapes by molecular dynamics (MD) simulation is challenging for such systems, especially when membrane recognition involves complex lipids, e.g., phosphatidylinositol phosphates (PIPs). We combined coarse-grained MD simulations with umbrella sampling to quantify the binding of the well-explored GRP1 pleckstrin homology (PH) domain to model membranes containing PIP molecules. The experimentally observed preference of GRP1-PH for PIP3 over PIP2 was reproduced. Mutation of a key residue (K273A) within the canonical PIP-binding site significantly reduced the free energy of PIP binding. The presence of a noncanonical PIP-interaction site, observed experimentally in other PH domains but not previously in GRP1-PH, was also revealed. These studies demonstrate how combining coarse-grained simulations and umbrella sampling can unmask the molecular basis of the energetics of interactions between peripheral membrane proteins and complex cellular membranes.

SUBMITTER: Naughton FB 

PROVIDER: S-EPMC5593124 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

Association of Peripheral Membrane Proteins with Membranes: Free Energy of Binding of GRP1 PH Domain with Phosphatidylinositol Phosphate-Containing Model Bilayers.

Naughton Fiona B FB   Kalli Antreas C AC   Sansom Mark S P MS  

The journal of physical chemistry letters 20160317 7


Understanding the energetics of peripheral protein-membrane interactions is important to many areas of biophysical chemistry and cell biology. Estimating free-energy landscapes by molecular dynamics (MD) simulation is challenging for such systems, especially when membrane recognition involves complex lipids, e.g., phosphatidylinositol phosphates (PIPs). We combined coarse-grained MD simulations with umbrella sampling to quantify the binding of the well-explored GRP1 pleckstrin homology (PH) doma  ...[more]

Similar Datasets

| S-EPMC7000246 | biostudies-literature
| S-EPMC3241724 | biostudies-literature
| S-EPMC2211451 | biostudies-literature
| S-EPMC6584618 | biostudies-literature
| S-EPMC4336358 | biostudies-literature
| S-EPMC2444010 | biostudies-literature
| S-EPMC4265004 | biostudies-literature
| S-EPMC4403170 | biostudies-literature
| S-EPMC4336182 | biostudies-literature
| S-EPMC4223227 | biostudies-other