PDB2PQR: Expanding and Upgrading Automated Preparation of Biomolecular Structures for Molecular Simulations

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2007 May 10

PMID 17488841

Citations 876

Authors

Todd J Dolinsky

Paul Czodrowski

Hui Li

Jens E Nielsen

Jan H Jensen

Gerhard Klebe

Nathan A Baker

Affiliations

Soon will be listed here.

Abstract

Real-world observable physical and chemical characteristics are increasingly being calculated from the 3D structures of biomolecules. Methods for calculating pK(a) values, binding constants of ligands, and changes in protein stability are readily available, but often the limiting step in computational biology is the conversion of PDB structures into formats ready for use with biomolecular simulation software. The continued sophistication and integration of biomolecular simulation methods for systems- and genome-wide studies requires a fast, robust, physically realistic and standardized protocol for preparing macromolecular structures for biophysical algorithms. As described previously, the PDB2PQR web server addresses this need for electrostatic field calculations (Dolinsky et al., Nucleic Acids Research, 32, W665-W667, 2004). Here we report the significantly expanded PDB2PQR that includes the following features: robust standalone command line support, improved pK(a) estimation via the PROPKA framework, ligand parameterization via PEOE_PB charge methodology, expanded set of force fields and easily incorporated user-defined parameters via XML input files, and improvement of atom addition and optimization code. These features are available through a new web interface (http://pdb2pqr.sourceforge.net/), which offers users a wide range of options for PDB file conversion, modification and parameterization.

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References

Berman H, Westbrook J, Feng Z, Gilliland G, Bhat T, Weissig H . The Protein Data Bank. Nucleic Acids Res. 1999; 28(1):235-42. PMC: 102472. DOI: 10.1093/nar/28.1.235. View

Sanner M . Python: a programming language for software integration and development. J Mol Graph Model. 2000; 17(1):57-61. View

Baker N, Sept D, Joseph S, Holst M, McCammon J . Electrostatics of nanosystems: application to microtubules and the ribosome. Proc Natl Acad Sci U S A. 2001; 98(18):10037-41. PMC: 56910. DOI: 10.1073/pnas.181342398. View

Dolinsky T, Nielsen J, McCammon J, Baker N . PDB2PQR: an automated pipeline for the setup of Poisson-Boltzmann electrostatics calculations. Nucleic Acids Res. 2004; 32(Web Server issue):W665-7. PMC: 441519. DOI: 10.1093/nar/gkh381. View

Baker N . Improving implicit solvent simulations: a Poisson-centric view. Curr Opin Struct Biol. 2005; 15(2):137-43. DOI: 10.1016/j.sbi.2005.02.001. View

Gordon J, Myers J, Folta T, Shoja V, Heath L, Onufriev A . H++: a server for estimating pKas and adding missing hydrogens to macromolecules. Nucleic Acids Res. 2005; 33(Web Server issue):W368-71. PMC: 1160225. DOI: 10.1093/nar/gki464. View

Case D, Cheatham 3rd T, Darden T, Gohlke H, Luo R, Merz Jr K . The Amber biomolecular simulation programs. J Comput Chem. 2005; 26(16):1668-88. PMC: 1989667. DOI: 10.1002/jcc.20290. View

Li H, Robertson A, Jensen J . Very fast empirical prediction and rationalization of protein pKa values. Proteins. 2005; 61(4):704-21. DOI: 10.1002/prot.20660. View

Davies M, Toseland C, Moss D, Flower D . Benchmarking pK(a) prediction. BMC Biochem. 2006; 7:18. PMC: 1513386. DOI: 10.1186/1471-2091-7-18. View

10.

Czodrowski P, Dramburg I, Sotriffer C, Klebe G . Development, validation, and application of adapted PEOE charges to estimate pKa values of functional groups in protein-ligand complexes. Proteins. 2006; 65(2):424-37. DOI: 10.1002/prot.21110. View

11.

Tan C, Yang L, Luo R . How well does Poisson-Boltzmann implicit solvent agree with explicit solvent? A quantitative analysis. J Phys Chem B. 2006; 110(37):18680-7. DOI: 10.1021/jp063479b. View

12.

Roux B, Simonson T . Implicit solvent models. Biophys Chem. 2006; 78(1-2):1-20. DOI: 10.1016/s0301-4622(98)00226-9. View

13.

Warshel A, Sharma P, Kato M, Parson W . Modeling electrostatic effects in proteins. Biochim Biophys Acta. 2006; 1764(11):1647-76. DOI: 10.1016/j.bbapap.2006.08.007. View

14.

Li X, Jacobson M, Zhu K, Zhao S, Friesner R . Assignment of polar states for protein amino acid residues using an interaction cluster decomposition algorithm and its application to high resolution protein structure modeling. Proteins. 2006; 66(4):824-37. DOI: 10.1002/prot.21125. View

15.

Czodrowski P, Sotriffer C, Klebe G . Protonation changes upon ligand binding to trypsin and thrombin: structural interpretation based on pK(a) calculations and ITC experiments. J Mol Biol. 2007; 367(5):1347-56. DOI: 10.1016/j.jmb.2007.01.022. View

16.

Czodrowski P, Sotriffer C, Klebe G . Atypical protonation states in the active site of HIV-1 protease: a computational study. J Chem Inf Model. 2007; 47(4):1590-8. DOI: 10.1021/ci600522c. View

17.

Vriend G . WHAT IF: a molecular modeling and drug design program. J Mol Graph. 1990; 8(1):52-6, 29. DOI: 10.1016/0263-7855(90)80070-v. View

18.

MacKerell A, Bashford D, Bellott M, Dunbrack R, Evanseck J, Field M . All-atom empirical potential for molecular modeling and dynamics studies of proteins. J Phys Chem B. 2014; 102(18):3586-616. DOI: 10.1021/jp973084f. View

19.

Honig B, Nicholls A . Classical electrostatics in biology and chemistry. Science. 1995; 268(5214):1144-9. DOI: 10.1126/science.7761829. View

20.

Humphrey W, Dalke A, Schulten K . VMD: visual molecular dynamics. J Mol Graph. 1996; 14(1):33-8, 27-8. DOI: 10.1016/0263-7855(96)00018-5. View