Computational prediction of kink properties of helices in membrane proteins
Journal
Journal of Computer-Aided Molecular Design
Journal Volume
28
Journal Issue
2
Pages
99-109
Date Issued
2014
Author(s)
Chi-Ming Chen
Abstract
We have combined molecular dynamics simulations and fold identification procedures to investigate the structure of 696 kinked and 120 unkinked transmembrane (TM) helices in the PDBTM database. Our main aim of this study is to understand the formation of helical kinks by simulating their quasi-equilibrium heating processes, which might be relevant to the prediction of their structural features. The simulated structural features of these TM helices, including the position and the angle of helical kinks, were analyzed and compared with statistical data from PDBTM. From quasi-equilibrium heating processes of TM helices with four very different relaxation time constants, we found that these processes gave comparable predictions of the structural features of TM helices. Overall, 95 % of our best kink position predictions have an error of no more than two residues and 75 % of our best angle predictions have an error of less than 15°. Various structure assessments have been carried out to assess our predicted models of TM helices in PDBTM. Our results show that, in 696 predicted kinked helices, 70 % have a RMSD less than 2 Å, 71 % have a TM-score greater than 0.5, 69 % have a MaxSub score greater than 0.8, 60 % have a GDT-TS score greater than 85, and 58 % have a GDT-HA score greater than 70. For unkinked helices, our predicted models are also highly consistent with their crystal structure. These results provide strong supports for our assumption that kink formation of TM helices in quasi-equilibrium heating processes is relevant to predicting the structure of TM helices.
Subjects
Computational prediction | Fold identification | Helical kinks | Molecular dynamics simulation | Quasi-equilibrium heating
Publisher
Springer Nature
Type
journal article