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A potential smoothing algorithm accurately predicts transmembrane helix packing

Nature Structural Biology volume 6, pages 50–55 (1999)Cite this article

An Erratum to this article was published on 01 February 1999

Abstract

Potential smoothing, a deterministic analog of stochastic simulated annealing, is a powerful paradigm for the solution of conformational search problems that require extensive sampling, and should be a useful tool in computational approaches to structure prediction and refinement. A novel potential smoothing and search (PSS) algorithm has been developed and applied to predict the packing of transmembrane helices. The highlight of this method is the efficient manner in which it circumvents the combinatorial explosion associated with the large number of minima on multidimensional potential energy surfaces in order to converge to the global energy minimum. Here we show how our potential smoothing and search method succeeds in finding the global minimum energy structure for the glycophorin A (GpA) transmembrane helix dimer by optimizing interhelical van der Waals interactions over rigid and semi–rigid helices. Structures obtained from our ab initio predictions are in close agreement with recent experimental data.

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Figure 1: One–dimensional schematic of the effect of a smoothing protocol on a potential energy surface.
Figure 2: Schematic of a more realistic potential smoothing protocol for molecular search problems.
Figure 3: Schematic of a helix dimer illustrating the method used to compute helix packing parameters.
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Acknowledgements

We thank E. Huang for useful discussions. This work was supported by a grant from the DOE Environmental Science Management Program.

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Authors and Affiliations

  1. Center for Molecular Design, Institute for Biomedical Computing, Washington University School of Medicine, St. Louis , 63110, Missouri, USA

    Rohit V. Pappu & Garland R. Marshall

  2. Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, 63110, Missouri, USA

    Jay W. Ponder

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  1. Rohit V. Pappu
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Correspondence to Jay W. Ponder.

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Pappu, R., Marshall, G. & Ponder, J. A potential smoothing algorithm accurately predicts transmembrane helix packing. Nat Struct Mol Biol 6, 50–55 (1999). https://doi.org/10.1038/4922

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