BIOPHYSICAL THEORY AND MODELING |
Membrane Assembly of Simple Helix Homo-Oligomers Studied via
Molecular Dynamics Simulations
Lintao Bu 1, Wonpil Im 2 and Charles L. Brooks 3*
1 The Scripps Research Institute
2 University of Kansas
3 The Scripps Research Inst.
* To whom correspondence should be addressed. E-mail: brooks{at}scripps.edu.
Submitted on August 14, 2006
Revised on October 16, 2006
Accepted on 20 October 2006
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Abstract |
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The assembly of simple transmembrane helix homo-oligomers is studied by combining a generalized Born implicit membrane model with replica exchange molecular dynamics simulations to sample the conformational space of various oligomerization states and the native oligomeric conformation. Our approach is applied to predict the structures of transmembrane helices of three proteins - glycophorin A, the M2 proton channel and phospholamban, using only peptide sequence and the native oligomerization state information. In every case, the methodology reproduces native conformations that are in good agreement with available experimental structural data. Thus, our method should be useful in the prediction of native structures of transmembrane domains of other peptides. When we ignore the experimental constraint on the native oligomerization state and attempt de novo prediction of the structure and oligomerization state based only on sequence and simple energetic considerations, we identify the pentamer as the most stable oligomer for phospholamban. However, for glycophorin A and the M2 proton channel, we tend to predict higher oligomers as more stable. Our studies demonstrate that reliable predictions of the structure of transmembrane helical oligomers can be achieved when the observed oligomerization state is imposed as a constraint, but that further efforts are needed for the de novo prediction of both structure and oligomeric state.
Key Words:
M2 proton channel, glycophorin A, helix association, implicit solvation, phospholamban, replica-exchange molecular dynamics
