Hydrophobicity of protein surfaces: Separating geometry from chemistry

doi:10.1073/pnas.0708088105

Hydrophobicity of protein surfaces: Separating geometry from chemistry

*Department of Chemical Engineering, Princeton University, Princeton, NJ 08544; and
^†Department of Chemistry and Biochemistry and Institute for Computational Engineering and Sciences, University of Texas, Austin, TX 78712

Edited by Frank H. Stillinger, Princeton University, Princeton, NJ, and approved December 21, 2007 (received for review August 28, 2007)

Abstract

To better understand the role of surface chemical heterogeneity in natural nanoscale hydration, we study via molecular dynamics simulation the structure and thermodynamics of water confined between two protein-like surfaces. Each surface is constructed to have interactions with water corresponding to those of the putative hydrophobic surface of a melittin dimer, but is flattened rather than having its native “cupped” configuration. Furthermore, peripheral charged groups are removed. Thus, the role of a rough surface topography is removed, and results can be productively compared with those previously observed for idealized, atomically smooth hydrophilic and hydrophobic flat surfaces. The results indicate that the protein surface is less hydrophobic than the idealized counterpart. The density and compressibility of water adjacent to a melittin dimer is intermediate between that observed adjacent to idealized hydrophobic or hydrophilic surfaces. We find that solvent evacuation of the hydrophobic gap (cavitation) between dimers is observed when the gap has closed to sterically permit a single water layer. This cavitation occurs at smaller pressures and separations than in the case of idealized hydrophobic flat surfaces. The vapor phase between the melittin dimers occupies a much smaller lateral region than in the case of the idealized surfaces; cavitation is localized in a narrow central region between the dimers, where an apolar amino acid is located. When that amino acid is replaced by a polar residue, cavitation is no longer observed.

Footnotes

^‡To whom correspondence should be addressed. E-mail: pdebene{at}princeton.edu
Author contributions: P.J.R. and P.G.D. designed research; N.G. and C.F.L. performed research; N.G., C.F.L., P.J.R., and P.G.D. analyzed data; and N.G., C.F.L., P.J.R., and P.G.D. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0708088105/DC1.
↵ § We obtain similar results if we define a cylindrical volume with radius of 0.7 nm or if we use a “cylinder” with an ellipsoidal base of radii a = 0.3 nm and b = 0.7 nm. A cylindrical volume with radius 1nm results in a sampling space that is too large and molecules from “bulk” water confound the statistics.
↵ ¶ The CN of a given molecule is defined as the number of neighbor oxygen atoms within a sphere of radius 0.32 nm centered at the oxygen atom of a central molecule. Oxygen atoms of the melittin dimers are also included in the calculations.