Hydrophobicity of protein surfaces: Separating geometry from chemistry

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.confinement ͉ water ͉ biopolymer ͉ compressibility ͉ cavitation I t has long been accepted that the hydrophobic effect plays a key role in the stability of compact native protein structures (1-3). The protein contains hydrophobic regions which associate, at least in part, due to the favorable solvent-mediated free energy of aggregation of nonpolar moieties in an aqueous environment (2, 4, 5). Although experimental studies (6) suggest that this rationalization is valid, and theoretical work using model systems and realistic protein structures (7) confirms such observations, much is still unknown about the role and behavior of water near proteins and how the aqueous solvent contributes to protein structural stability at the molecular level. The main focus of the present work is to contribute to the understanding of water near, and between, nominally hydrophobic, but realistic, protein surfaces.When one turns to the molecular details of the mechanism of nonpolar aggregation in water, the picture is still not completely clear. The two limiting scenarios for events such as protein folding and directed self-assembly are summarized well in ref. 8, in the context of protein folding. The basic feature distinguishing these scenarios is the relationship between solute dehydration and solute spatial approach. In the traditional view, water is gradually reduced within and between the associating regions in a manner that is concerted with their spatial approach. In an alternative cavitation sce...

Characterizing hydrophobicity of interfaces by using cavity formation, solute binding, and water correlations

“…Characterization based on some of these signatures can be extended to interfaces of complex nanoscopic objects such as proteins (49,69) and biomolecules or nanoparticles, and has the potential to provide a fundamental understanding of a host of water-mediated interactions important in biological and colloidal self-assembly.…”

“…(54) show that the interface of large repulsive hydrophobic solutes is rough and flickering and broadened by capillary wave-like fluctuations. Giovambattista et al (48,49) show that water confined between hydrophobic plates is more compressible than in bulk water or between hydrophilic surfaces. A picture of the hydrophobic-water interface that emerges from those studies is that hydration shells of hydrophobic solutes are soft, highly compressible, and characterized by enhanced density fluctuations (55).…”

Sparse Sampling of Water Density Fluctuations in Interfacial Environments

“…1,16,18,20 Fluctuations are particularly useful in characterizing the hydrophobicity of complex surfaces with molecular-level heterogeneities, wherein conventional macroscopic measures, such as the water droplet contact angle, break down. 45 Indeed, for the rugged, heterogenous surfaces of proteins, hydrophobicity depends not only on the chemistry of the underlying residues, 12,18,20,46 but also on the particular topography [47][48][49] and chemical pat-tern 12,[50][51][52][53] presented by the protein, and can depend non-trivially on the specific combination of the two. 39,40,[54][55][56] Fluctuations have previously been used to characterize the hydrophobicity of such complex surfaces using small (e.g., methane-sized) v, 12,46 wherein the fluctuations of interest can be estimated using equilibrium molecular simulations.…”

Dynamical perspective of protein-DNA interaction

“…Protein and DNA are two of the most important biomolecules in any living organism (1)(2)(3)(4)(5). DNA stores the genetic information, while protein takes care of executing and regulating the life processes.…”