CAVE: A package for detection and quantitative analysis of internal cavities in a system of overlapping balls: Application to proteins

We developed a software package (CAVE) in Fortran language to detect internal cavities in proteins which can be applied also to an arbitrary system of balls. The volume, the surface area and other quantitative characteristics of the cavities can be calculated. The code is based on the recently suggested enveloping triangulation algorithm [J. Busa et al., J. Comp. Chem. 30 (2009) 346] for computing volume and surface area of the cavity by analytical equations. Different standard sets of atomic radii can be used. The PDB compatible file containing the atomic coordinates must be stored on the disk in advance. Testing of the code on different proteins and artificial ball systems showed efficiency and accuracy of the algorithm. The program is fast. It can handle a system of several thousands of balls in the order of seconds on contemporary PC's. The code is open source and free.

[1]  K. D. Gibson,et al.  Exact calculation of the volume and surface area of fused hard-sphere molecules with unequal atomic radii , 1987 .

[2]  P Argos,et al.  Intramolecular cavities in globular proteins. , 1994, Protein engineering.

[3]  B Honig,et al.  Internal cavities and buried waters in globular proteins. , 1986, Biochemistry.

[4]  Gerhard Hummer,et al.  Cooperative water filling of a nonpolar protein cavity observed by high-pressure crystallography and simulation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Ulrich H E Hansmann,et al.  Parallel tempering simulations of HP‐36 , 2003, Proteins.

[6]  M. L. Connolly.  Analytical molecular surface calculation , 1983 .

[7]  Shura Hayryan,et al.  Efficient combination of Wang–Landau and transition matrix Monte Carlo methods for protein simulations , 2007, J. Comput. Chem..

[8]  C. Chothia,et al.  Hydrophobic bonding and accessible surface area in proteins , 1974, Nature.

[9]  H. Edelsbrunner,et al.  Anatomy of protein pockets and cavities: Measurement of binding site geometry and implications for ligand design , 1998, Protein science : a publication of the Protein Society.

[10]  David S. Wishart,et al.  VADAR: a web server for quantitative evaluation of protein structure quality , 2003, Nucleic Acids Res..

[11]  P. Argos,et al.  Cavities and packing at protein interfaces , 1994, Protein science : a publication of the Protein Society.

[12]  Brian W Matthews.  Racemic crystallography—Easy crystals and easy structures: What's not to like? , 2009, Protein science : a publication of the Protein Society.

[13]  Shura Hayryan,et al.  Enveloping triangulation method for detecting internal cavities in proteins and algorithm for computing their surface areas and volumes , 2009, J. Comput. Chem..

[14]  M L Connolly,et al.  The molecular surface package. , 1993, Journal of molecular graphics.

[15]  F M Richards,et al.  Areas, volumes, packing and protein structure. , 1977, Annual review of biophysics and bioengineering.

[16]  A. Fersht,et al.  Contribution of hydrophobic interactions to protein stability , 1988, Nature.

[17]  Harold A. Scheraga,et al.  Volume of the intersection of three spheres of unequal size: a simplified formula , 1987 .

[18]  P. Gonçalves,et al.  Free energy of solvation from molecular dynamics simulation applying Voronoi-Delaunay triangulation to the cavity creation. , 2005, The Journal of chemical physics.

[19]  Ulrich H. E. Hansmann,et al.  SMMP) A modern package for simulation of proteins , 2001 .

[20]  Raghavan Varadarajan,et al.  A Procedure for Detection and Quantitation of Cavity Volumes in Proteins , 2002, The Journal of Biological Chemistry.

[21]  Michel Petitjean,et al.  On the analytical calculation of van der Waals surfaces and volumes: Some numerical aspects , 1994, J. Comput. Chem..

[22]  Ulrich H. E. Hansmann,et al.  An enhanced version of SMMP - open-source software package for simulation of proteins , 2006, Comput. Phys. Commun..

[23]  Shura Hayryan,et al.  A new analytical method for computing solvent‐accessible surface area of macromolecules and its gradients , 2005, J. Comput. Chem..

[24]  P. Axelsen,et al.  Buried water in homologous serine proteases. , 1992, Biochemistry.

[25]  R. Laskowski.  SURFNET: a program for visualizing molecular surfaces, cavities, and intermolecular interactions. , 1995, Journal of molecular graphics.

[26]  B. Lee,et al.  The interpretation of protein structures: estimation of static accessibility. , 1971, Journal of molecular biology.

[27]  S Subramaniam,et al.  Analytical shape computation of macromolecules: I. molecular area and volume through alpha shape , 1998, Proteins.

[28]  B P Schoenborn,et al.  Structure of alkaline metmyoglobin-xenon complex. , 1969, Journal of molecular biology.

[29]  Dirk Bakowies,et al.  Water in protein cavities: A procedure to identify internal water and exchange pathways and application to fatty acid‐binding protein , 2002, Proteins.

[30]  I. Kuntz,et al.  Cavities in proteins: structure of a metmyoglobin-xenon complex solved to 1.9 A. , 1984, Biochemistry.

[31]  Gerhard Hummer,et al.  Structural rigidity of a large cavity-containing protein revealed by high-pressure crystallography. , 2007, Journal of molecular biology.

[32]  Brian W Matthews,et al.  A review about nothing: Are apolar cavities in proteins really empty? , 2009, Protein science : a publication of the Protein Society.

[33]  Michael L. Connolly,et al.  Computation of molecular volume , 1985 .

[34]  A. Fersht,et al.  Energetics of complementary side-chain packing in a protein hydrophobic core. , 1989, Biochemistry.

[35]  H Edelsbrunner,et al.  Analytical shape computation of macromolecules: II. Inaccessible cavities in proteins , 1998, Proteins.

[36]  B. Matthews,et al.  A cavity-containing mutant of T4 lysozyme is stabilized by buried benzene , 1993, Nature.

[37]  J Hermans,et al.  Hydrophilicity of cavities in proteins , 1996, Proteins.

[38]  R Abagyan,et al.  The contour-buildup algorithm to calculate the analytical molecular surface. , 1996, Journal of structural biology.

[39]  Herbert Edelsbrunner,et al.  Triangulating the Surface of a Molecule , 1996, Discret. Appl. Math..

[40]  R Abagyan,et al.  Evaluating the energetics of empty cavities and internal mutations in proteins , 1997, Protein science : a publication of the Protein Society.

[41]  Michael L. Connolly,et al.  Molecular surface Triangulation , 1985 .

[42]  Ericka Stricklin-Parker,et al.  Ann , 2005 .

[43]  Ján Plávka,et al.  ARVO: A Fortran package for computing the solvent accessible surface area and the excluded volume of overlapping spheres via analytic equations , 2005, Comput. Phys. Commun..

[44]  S. Boxer,et al.  Anatomy and dynamics of a ligand-binding pathway in myoglobin: the roles of residues 45, 60, 64, and 68. , 1994, Biochemistry.

[45]  M. Noble,et al.  Comparison of the refined crystal structures of liganded and unliganded chicken, yeast and trypanosomal triosephosphate isomerase. , 1992, Journal of molecular biology.

[46]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[47]  T. Richmond,et al.  Solvent accessible surface area and excluded volume in proteins. Analytical equations for overlapping spheres and implications for the hydrophobic effect. , 1984, Journal of molecular biology.

[48]  G Vriend,et al.  The effect of cavity-filling mutations on the thermostability of Bacillus stearothermophilus neutral protease. , 1992, Protein engineering.

[49]  R Nussinov,et al.  A set of van der Waals and coulombic radii of protein atoms for molecular and solvent‐accessible surface calculation, packing evaluation, and docking , 1998, Proteins.

[50]  M. L. Connolly.  Solvent-accessible surfaces of proteins and nucleic acids. , 1983, Science.

[52]  B. Matthews,et al.  Similar hydrophobic replacements of Leu99 and Phe153 within the core of T4 lysozyme have different structural and thermodynamic consequences. , 1993, Journal of molecular biology.

[53]  J. Thornton,et al.  Buried waters and internal cavities in monomeric proteins , 1994, Protein science : a publication of the Protein Society.

[54]  A. Shrake,et al.  Environment and exposure to solvent of protein atoms. Lysozyme and insulin. , 1973, Journal of molecular biology.