DelPhi: a comprehensive suite for DelPhi software and associated resources

BackgroundAccurate modeling of electrostatic potential and corresponding energies becomes increasingly important for understanding properties of biological macromolecules and their complexes. However, this is not an easy task due to the irregular shape of biological entities and the presence of water and mobile ions.ResultsHere we report a comprehensive suite for the well-known Poisson-Boltzmann solver, DelPhi, enriched with additional features to facilitate DelPhi usage. The suite allows for easy download of both DelPhi executable files and source code along with a makefile for local installations. The users can obtain the DelPhi manual and parameter files required for the corresponding investigation. Non-experienced researchers can download examples containing all necessary data to carry out DelPhi runs on a set of selected examples illustrating various DelPhi features and demonstrating DelPhi’s accuracy against analytical solutions.ConclusionsDelPhi suite offers not only the DelPhi executable and sources files, examples and parameter files, but also provides links to third party developed resources either utilizing DelPhi or providing plugins for DelPhi. In addition, the users and developers are offered a forum to share ideas, resolve issues, report bugs and seek help with respect to the DelPhi package. The resource is available free of charge for academic users from URL: http://compbio.clemson.edu/DelPhi.php

[1]  Michael Nilges,et al.  BIOINFORMATICS APPLICATIONS NOTE doi:10.1093/bioinformatics/btl655 Structural bioinformatics Biskit—A software platform for structural bioinformatics , 2006 .

[2]  D. Peter Tieleman,et al.  Modifying the OPLS‐AA force field to improve hydration free energies for several amino acid side chains using new atomic charges and an off‐plane charge model for aromatic residues , 2007, J. Comput. Chem..

[3]  Bert L de Groot,et al.  Secondary structure propensities in peptide folding simulations: a systematic comparison of molecular mechanics interaction schemes. , 2009, Biophysical journal.

[4]  Michael J. Holst,et al.  Adaptive multilevel finite element solution of the Poisson–Boltzmann equation I. Algorithms and examples , 2001 .

[5]  David N. LeBard,et al.  Protein-water electrostatics and principles of bioenergetics. , 2010, Physical chemistry chemical physics : PCCP.

[6]  Magdalena A. Jonikas,et al.  Distinct contribution of electrostatics, initial conformational ensemble, and macromolecular stability in RNA folding , 2007, Proceedings of the National Academy of Sciences.

[7]  Zhe Zhang,et al.  Computational analysis of missense mutations causing Snyder‐Robinson syndrome , 2010, Human mutation.

[8]  Huan-Xiang Zhou,et al.  Effects of pH, salt, and macromolecular crowding on the stability of FK506-binding protein: an integrated experimental and theoretical study. , 2005, Journal of molecular biology.

[9]  B. Honig,et al.  Calculation of the total electrostatic energy of a macromolecular system: Solvation energies, binding energies, and conformational analysis , 1988, Proteins.

[10]  R Nussinov,et al.  Explicit and implicit water simulations of a β‐hairpin peptide , 1999, Proteins.

[11]  R. Zhou Free energy landscape of protein folding in water: Explicit vs. implicit solvent , 2003, Proteins.

[12]  Steven S Plotkin,et al.  Electrostatics in the stability and misfolding of the prion protein: salt bridges, self energy, and solvation. , 2010, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[13]  Emil Alexov,et al.  On the electrostatic component of protein-protein binding free energy , 2008, PMC biophysics.

[14]  S. Harvey Treatment of electrostatic effects in macromolecular modeling , 1989, Proteins.

[15]  K. Sharp,et al.  Electrostatic interactions in macromolecules: theory and applications. , 1990, Annual review of biophysics and biophysical chemistry.

[16]  J. Skolnick,et al.  TM-align: a protein structure alignment algorithm based on the TM-score , 2005, Nucleic acids research.

[17]  B. Honig,et al.  A rapid finite difference algorithm, utilizing successive over‐relaxation to solve the Poisson–Boltzmann equation , 1991 .

[18]  Y. Sugita,et al.  Comparisons of force fields for proteins by generalized-ensemble simulations , 2004 .

[19]  Emil Alexov,et al.  In silico modeling of pH‐optimum of protein–protein binding , 2011, Proteins.

[20]  Emil Alexov,et al.  Using DelPhi capabilities to mimic protein's conformational reorganization with amino acid specific dielectric constants. , 2013, Communications in computational physics.

[21]  B. Honig,et al.  Classical electrostatics in biology and chemistry. , 1995, Science.

[22]  J. Trylska,et al.  Continuum molecular electrostatics, salt effects, and counterion binding—A review of the Poisson–Boltzmann theory and its modifications , 2008, Biopolymers.

[23]  B Honig,et al.  Calculation of electrostatic effects at the amino terminus of an alpha helix. , 1994, Biophysical journal.

[24]  Emil Alexov,et al.  Poisson-Boltzmann calculations of nonspecific salt effects on protein-protein binding free energies. , 2007, Biophysical journal.

[25]  K A Dill,et al.  Explicit-water molecular dynamics study of a short-chain 3,3 ionene in solutions with sodium halides. , 2009, Journal of Chemical Physics.

[26]  K. Sharp,et al.  On the calculation of pKas in proteins , 1993, Proteins.

[27]  Nathan A. Baker,et al.  Poisson-Boltzmann Methods for Biomolecular Electrostatics , 2004, Numerical Computer Methods, Part D.

[28]  Richard A. Friesner,et al.  Numerical solution of the Poisson-Boltzmann equation using tetrahedral finite-element meshes , 1997, J. Comput. Chem..

[29]  J. Ponder,et al.  Force fields for protein simulations. , 2003, Advances in protein chemistry.

[30]  Jan H. Jensen,et al.  Calculating pH and salt dependence of protein-protein binding. , 2008, Current pharmaceutical biotechnology.

[31]  F. Avbelj,et al.  Role of main-chain electrostatics, hydrophobic effect and side-chain conformational entropy in determining the secondary structure of proteins. , 1998, Journal of molecular biology.

[32]  KALJU KAHN,et al.  Parameterization of OPLS–AA force field for the conformational analysis of macrocyclic polyketides , 2002, J. Comput. Chem..

[33]  Zhe Zhang,et al.  In Silico and In Vitro Investigations of the Mutability of Disease-Causing Missense Mutation Sites in Spermine Synthase , 2011, PloS one.

[34]  A. Warshel,et al.  Calculations of electrostatic energies in proteins. The energetics of ionized groups in bovine pancreatic trypsin inhibitor. , 1985, Journal of molecular biology.

[35]  Emil Alexov,et al.  Calculation of pKas in RNA: on the structural origins and functional roles of protonated nucleotides. , 2007, Journal of molecular biology.

[36]  Wilfred F. van Gunsteren,et al.  An improved OPLS–AA force field for carbohydrates , 2002, J. Comput. Chem..

[37]  Burkhard Dünweg,et al.  Implicit and explicit solvent models for the simulation of a single polymer chain in solution: Lattice Boltzmann versus Brownian dynamics. , 2009, The Journal of chemical physics.

[38]  Guo-Wei Wei,et al.  Highly accurate biomolecular electrostatics in continuum dielectric environments , 2008, J. Comput. Chem..

[39]  Conrad C. Huang,et al.  UCSF Chimera—A visualization system for exploratory research and analysis , 2004, J. Comput. Chem..

[40]  Barry Honig,et al.  Focusing of electric fields in the active site of Cu‐Zn superoxide dismutase: Effects of ionic strength and amino‐acid modification , 1986, Proteins.

[41]  Emil Alexov,et al.  Numerical calculations of the pH of maximal protein stability. The effect of the sequence composition and three-dimensional structure. , 2003, European journal of biochemistry.

[42]  E. Alexov,et al.  Combining conformational flexibility and continuum electrostatics for calculating pK(a)s in proteins. , 2002, Biophysical journal.

[43]  Emil Alexov,et al.  Rapid grid‐based construction of the molecular surface and the use of induced surface charge to calculate reaction field energies: Applications to the molecular systems and geometric objects , 2002, J. Comput. Chem..

[44]  Ray Luo,et al.  How well does Poisson-Boltzmann implicit solvent agree with explicit solvent? A quantitative analysis. , 2006, The journal of physical chemistry. B.

[45]  Zhe Zhang,et al.  On the role of electrostatics in protein–protein interactions , 2011, Physical biology.

[46]  Jianpeng Ma,et al.  CHARMM: The biomolecular simulation program , 2009, J. Comput. Chem..

[47]  Emil Alexov,et al.  A missense mutation in CLIC2 associated with intellectual disability is predicted by in silico modeling to affect protein stability and dynamics , 2011, Proteins.

[48]  Wei Yang,et al.  Developing hybrid approaches to predict pKa values of ionizable groups , 2011, Proteins.

[49]  J. Andrew Grant,et al.  A smooth permittivity function for Poisson–Boltzmann solvation methods , 2001, J. Comput. Chem..

[50]  B. Roux,et al.  Atomic Radii for Continuum Electrostatics Calculations on Nucleic Acids , 2002 .

[51]  Yong Duan,et al.  Comparison between Generalized-Born and Poisson–Boltzmann methods in physics-based scoring functions for protein structure prediction , 2005, Journal of molecular modeling.

[52]  J. A. McCammon,et al.  Solving the finite difference linearized Poisson‐Boltzmann equation: A comparison of relaxation and conjugate gradient methods , 1989 .

[53]  Kalliopi K. Patapati,et al.  Three force fields' views of the 3(10) helix. , 2011, Biophysical journal.

[54]  Sarah L. Williams,et al.  Progress in the prediction of pKa values in proteins , 2011, Proteins.

[55]  Wilfred F van Gunsteren,et al.  Explicit-solvent molecular dynamics simulations of the polysaccharide schizophyllan in water. , 2007, Biophysical journal.

[56]  K Schulten,et al.  VMD: visual molecular dynamics. , 1996, Journal of molecular graphics.

[57]  Justin R. Spaeth,et al.  A comparison of implicit- and explicit-solvent simulations of self-assembly in block copolymer and solute systems. , 2011, The Journal of chemical physics.

[58]  Barry Honig,et al.  Extending the Applicability of the Nonlinear Poisson−Boltzmann Equation: Multiple Dielectric Constants and Multivalent Ions† , 2001 .

[59]  B. Honig,et al.  On the calculation of electrostatic interactions in proteins. , 1985, Journal of molecular biology.

[60]  Patrik Rydberg,et al.  Implicit versus explicit solvent in free energy calculations of enzyme catalysis: Methyl transfer catalyzed by catechol O-methyltransferase. , 2006, The Journal of chemical physics.

[61]  Michael J. Holst,et al.  Adaptive multilevel finite element solution of the Poisson-Boltzmann equation II. Refinement at solvent-accessible surfaces in biomolecular systems , 2000, J. Comput. Chem..

[62]  B Honig,et al.  On the pH dependence of protein stability. , 1993, Journal of molecular biology.