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Biophys. J. BioFAST: First Published February 3, 2006. doi:10.1529/biophysj.105.073171
© 2006 by the Biophysical Society.

A more recent version of this article appeared on May 1, 2006.
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BIOPHYSICAL THEORY AND MODELING

Towards the understanding of MNEI sweetness from hydration map surfaces

Alfonso De Simone 1, Roberta Spadaccini 2, Pier Andrea Temussi 3 and Franca Fraternali 1*

1 National Institute for Medical Research Mill Hill London
2 EMBL Heidelberg
3 Universita' di Napoli

* To whom correspondence should be addressed. E-mail: ffranca{at}nimr.mrc.ac.uk.

Submitted on August 24, 2005
Revised on October 12, 2005
Accepted on 12 January 2006


  Abstract
The binding mechanism of sweet proteins to their receptor, a GPCR protein, is not supported by direct structural information. In principle, the key groups responsible for biological activity (glucophores), can be localized on a small structural unit (sweet finger), or spread on a larger surface area. A recently proposed model, called 'wedge model', implies a large surface of interaction with the receptor. In order to explore this model in greater detail, it is necessary to examine the physico-chemical features of the surfaces of sweet proteins, since their interaction with the receptor, with respect to that of small sweeteners, is more dependent on general physico-chemical properties of the interface, such as electrostatic potential and hydration. In the present study we performed exhaustive MD simulations in explicit water of the sweet protein MNEI and of its structural mutant G16A, whose sweetness is one order of magnitude lower than that of MNEI. Solvent density and self-diffusion calculated from MD simulations suggest a likely area of interaction delimited by four stretches arranged as a tetrahedron whose shape is complementary to that of a cavity on the surface of the receptor, in agreement with the wedge model. The suggested area of interaction is amazingly consistent with known mutagenesis data. In addition, the asymmetric hydration of the only helix in both proteins, hints at a specific role for this secondary structure element in orienting the protein during the binding process.

Key Words: NMR, hydration sites, molecular dynamics, monellin, solvent self diffusion map, sweet proteins




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Copyright © 2006 by the Biophysical Society.