Volumetric properties of hydrated peptides: Voronoi-Delaunay analysis of molecular simulation runs.

The study of hydration, folding, and interaction of proteins by volumetric measurements has been promoted by recent advances in the development of highly sensitive instrumentations. However, the separation of the measured apparent volumes into contributions from the protein and the hydration water, V(app) = V(int) + ΔV, is still challenging, even with the detailed microscopic structural information from molecular simulations. By the examples of the amyloidogenic polypeptides hIAPP and Aβ42 in aqueous solution, we analyze molecular dynamics simulation runs for different temperatures, using the Voronoi-Delaunay tessellation method. This method allows a parameter free determination of the intrinsic volume V(int) of complex solute molecules without any additional assumptions. For comparison, we also use fused sphere calculations, which deliver van der Waals and solute accessible surface volumes as special cases. The apparent volume V(app) of the solute molecules is calculated by different approaches, using either a traditional distance based selection of hydration water or the construction of sequential Voronoi shells. We find an astonishing coincidence with the predictions of a simple empirical approach, which is based on experimentally determined amino acid side chain contributions (Biophys. Chem.1999, 82, 35). The intrinsic volumes of the polypeptides are larger than their apparent volumes and also increase with temperature. This is due to a negative contribution of the hydration water ΔV to the apparent volume. The absolute value of this contribution is less than 10% of the intrinsic volume for both molecules and decreases with temperature. Essential volumetric differences between hydration water and bulk water are observed in the nearest neighborhood of the solute only, practically in the first two Delaunay sublayers of the first Voronoi shell. This also helps to understand the pressure dependence of the partial molar volumes of proteins.

[1]  Michael Nilges,et al.  Shelling the Voronoi interface of protein–protein complexes reveals patterns of residue conservation, dynamics, and composition , 2009, Proteins.

[2]  Piero Procacci,et al.  A General Algorithm for Computing Voronoi Volumes - Application to the Hydrated Crystal of Myoglobin , 1992 .

[3]  O. Steinhauser,et al.  Simulation studies of the protein-water interface. II. Properties at the mesoscopic resolution. , 2006, The Journal of chemical physics.

[4]  Volumetric properties of human islet amyloid polypeptide in liquid water. , 2010, Physical chemistry chemical physics : PCCP.

[5]  N. Smolin,et al.  Pressure perturbation calorimetric studies of the solvation properties and the thermal unfolding of proteins in solution--experiments and theoretical interpretation. , 2006, Physical chemistry chemical physics : PCCP.

[6]  Mihaly Mezei.  Modified Proximity Criteria for the Analysis of the Solvation of a Polyfunctional Solute , 1988 .

[7]  H. Hinz,et al.  Response functions of proteins. , 2000, Biophysical chemistry.

[8]  Carl W David,et al.  Voronoi polyhedra as a tool for studying solvation structure , 1982 .

[9]  R. Winter,et al.  Volumetric Properties of Hydration Water , 2009 .

[10]  C. Royer,et al.  Volume, expansivity and isothermal compressibility changes associated with temperature and pressure unfolding of Staphylococcal nuclease. , 2001, Journal of molecular biology.

[11]  Michael Levitt,et al.  Nonpolar solutes enhance water structure within hydration shells while reducing interactions between them. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[12]  B M Pettitt,et al.  A Connected‐cluster of hydration around myoglobin: Correlation between molecular dynamics simulations and experiment , 1994, Proteins.

[13]  Deok-Soo Kim,et al.  Molecular surfaces on proteins via beta shapes , 2007, Comput. Aided Des..

[14]  E. Paci,et al.  Intrinsic compressibility and volume compression in solvated proteins by molecular dynamics simulation at high pressure. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[15]  N. Smolin,et al.  Formation of spanning water networks on protein surfaces via 2D percolation transition. , 2005, The journal of physical chemistry. B.

[16]  T. Straatsma,et al.  THE MISSING TERM IN EFFECTIVE PAIR POTENTIALS , 1987 .

[17]  J. Brandts,et al.  Determination of the volumetric properties of proteins and other solutes using pressure perturbation calorimetry. , 2002, Analytical biochemistry.

[18]  H. Edelsbrunner.  The union of balls and its dual shape , 1995 .

[19]  Marina L. Gavrilova,et al.  An algorithm for three‐dimensional Voronoi S‐network , 2006, J. Comput. Chem..

[20]  C. Royer,et al.  Towards a quantitative understanding of protein hydration and volumetric properties. , 2008, Chemphyschem : a European journal of chemical physics and physical chemistry.

[21]  G. Ullmann,et al.  McVol - A program for calculating protein volumes and identifying cavities by a Monte Carlo algorithm , 2010, Journal of molecular modeling.

[22]  T. Chalikian.  Volumetric properties of proteins. , 2003, Annual review of biophysics and biomolecular structure.

[23]  Roland Winter,et al.  Comparing the structural properties of human and rat islet amyloid polypeptide by MD computer simulations. , 2011, Biophysical chemistry.

[24]  H. Eugene Stanley,et al.  Equation of state of supercooled water simulated using the extended simple point charge intermolecular potential , 1997 .

[25]  Mihaly Mezei,et al.  Morphology of Voids in Molecular Systems. A Voronoi−Delaunay Analysis of a Simulated DMPC Membrane , 2004 .

[26]  A. Poupon.  Voronoi and Voronoi-related tessellations in studies of protein structure and interaction. , 2004, Current opinion in structural biology.

[27]  A. Cooper,et al.  Applications of pressure perturbation calorimetry in biophysical studies. , 2011, Biophysical chemistry.

[28]  O. Steinhauser,et al.  Global and local Voronoi analysis of solvation shells of proteins. , 2010, The Journal of chemical physics.

[29]  O. Steinhauser,et al.  On the collective network of ionic liquid/water mixtures. III. Structural analysis of ionic liquids on the basis of Voronoi decomposition. , 2009, The Journal of chemical physics.

[30]  A. Garcia,et al.  Studying pressure denaturation of a protein by molecular dynamics simulations , 2010, Proteins.

[31]  R. Winter,et al.  Pressure perturbation calorimetry: a new technique provides surprising results on the effects of co-solvents on protein solvation and unfolding behaviour. , 2004, Chemphyschem : a European journal of chemical physics and physical chemistry.

[32]  J Andrew McCammon,et al.  Structural and dynamic properties of water around acetylcholinesterase , 2002, Protein science : a publication of the Protein Society.

[33]  Heat capacity effects associated with the hydrophobic hydration and interaction of simple solutes: a detailed structural and energetical analysis based on molecular dynamics simulations. , 2004, The Journal of chemical physics.

[34]  R. Friesner,et al.  Evaluation and Reparametrization of the OPLS-AA Force Field for Proteins via Comparison with Accurate Quantum Chemical Calculations on Peptides† , 2001 .

[35]  C. Pierleoni,et al.  Molecular modeling and simulation of water near model micelles: diffusion, rotational relaxation and structure at the hydration interface. , 2006, The journal of physical chemistry. B.

[36]  Franz Aurenhammer,et al.  Power Diagrams: Properties, Algorithms and Applications , 1987, SIAM J. Comput..

[37]  F. Stillinger,et al.  Statistical geometry of particle packings. I. Algorithm for exact determination of connectivity, volume, and surface areas of void space in monodisperse and polydisperse sphere packings , 1997 .

[38]  D. Paschek,et al.  Gibbs ensemble simulation of water in spherical cavities , 2000 .

[39]  J L Finney,et al.  Calculation of protein volumes: an alternative to the Voronoi procedure. , 1982, Journal of molecular biology.

[40]  R. Winter,et al.  Cold- and pressure-induced dissociation of protein aggregates and amyloid fibrils. , 2008, Angewandte Chemie.

[41]  E. Paci.  High pressure simulations of biomolecules. , 2002, Biochimica et biophysica acta.

[42]  H. Hinz,et al.  Partial molar volumes of proteins: amino acid side-chain contributions derived from the partial molar volumes of some tripeptides over the temperature range 10-90 degrees C. , 1999, Biophysical chemistry.

[43]  R. Winter,et al.  Volume changes associated with guanidine hydrochloride, temperature, and ethanol induced unfolding of lysozyme. , 2010, The journal of physical chemistry. B.

[44]  C. Royer.  Revisiting volume changes in pressure-induced protein unfolding. , 2002, Biochimica et biophysica acta.

[45]  R. Winter,et al.  Intrinsic thermal expansivity and hydrational properties of amyloid peptide Abeta42 in liquid water. , 2008, The Journal of chemical physics.

[46]  G. Makhatadze,et al.  Universal convergence of the specific volume changes of globular proteins upon unfolding. , 2009, Biochemistry.

[47]  W. L. Jorgensen,et al.  Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids , 1996 .

[48]  Iosif I. Vaisman,et al.  Distance Dependence of Water Structure around Model Solutes , 1994 .

[49]  Deok-Soo Kim,et al.  Three-dimensional beta shapes , 2006, Comput. Aided Des..

[50]  Gerrit Groenhof,et al.  GROMACS: Fast, flexible, and free , 2005, J. Comput. Chem..

[51]  R. Winter,et al.  On the temperature--pressure free-energy landscape of proteins. , 2003, Chemphyschem : a European journal of chemical physics and physical chemistry.