Online citations, reference lists, and bibliographies.
← Back to Search

H++ 3.0: Automating PK Prediction And The Preparation Of Biomolecular Structures For Atomistic Molecular Modeling And Simulations

Ramu Anandakrishnan, Boris Aguilar, A. Onufriev
Published 2012 · Biology, Computer Science, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
The accuracy of atomistic biomolecular modeling and simulation studies depend on the accuracy of the input structures. Preparing these structures for an atomistic modeling task, such as molecular dynamics (MD) simulation, can involve the use of a variety of different tools for: correcting errors, adding missing atoms, filling valences with hydrogens, predicting pK values for titratable amino acids, assigning predefined partial charges and radii to all atoms, and generating force field parameter/topology files for MD. Identifying, installing and effectively using the appropriate tools for each of these tasks can be difficult for novice and time-consuming for experienced users. H++ (http://biophysics.cs.vt.edu/) is a free open-source web server that automates the above key steps in the preparation of biomolecular structures for molecular modeling and simulations. H++ also performs extensive error and consistency checking, providing error/warning messages together with the suggested corrections. In addition to numerous minor improvements, the latest version of H++ includes several new capabilities and options: fix erroneous (flipped) side chain conformations for HIS, GLN and ASN, include a ligand in the input structure, process nucleic acid structures and generate a solvent box with specified number of common ions for explicit solvent MD.
This paper references
10.1002/jcc.20290
The Amber biomolecular simulation programs
D. A. Case (2005)
10.1002/PROT.340200109
Intrinsic pKas of ionizable residues in proteins: An explicit solvent calculation for lysozyme
G. S. Del Buono (1994)
10.1038/nsb0902-646
Molecular dynamics simulations of biomolecules
M. Karplus (2002)
Interpretation of Protein Titration
C. Tanford (1972)
10.1110/ps.03504104
Sensitivity of molecular dynamics simulations to the choice of the X‐ray structure used to model an enzymatic reaction
Mireia Garcia-Viloca (2004)
On the Calculation of pK a 's in Proteins
A.-S Yang (1993)
10.1021/BI002740Q
A novel view of pH titration in biomolecules.
A. Onufriev (2001)
10.1021/JP960111D
Improving the Continuum Dielectric Approach to Calculating pKas of Ionizable Groups in Proteins
E. Demchuk (1996)
10.1021/JA01577A001
Theory of Protein Titration Curves. I. General Equations for Impenetrable Spheres
C. Tanford (1957)
10.1007/S10858-006-9003-3
Chemically accurate protein structures: Validation of protein NMR structures by comparison of measured and predicted pKa values
N. Powers (2006)
10.1110/ps.036335.108
A fast and accurate computational approach to protein ionization
V. Spassov (2008)
10.1038/sj.embor.7401160
Molecular simulations of protein dynamics: new windows on mechanisms in biology
G. Dodson (2008)
10.1006/JMBI.1994.1301
Prediction of pH-dependent properties of proteins.
J. Antosiewicz (1994)
10.1002/prot.20128
Constant‐pH molecular dynamics using continuous titration coordinates
M. Lee (2004)
10.1002/pro.19
A summary of the measured pK values of the ionizable groups in folded proteins
G. Grimsley (2009)
10.1007/3-540-31618-3_15
Implicit Solvent Electrostatics in Biomolecular Simulation
Nathan A. Baker (2006)
Molecular dynamics simulations of the Complete Satellite Tobacco Mosaic Virus. Structure
P L Freddolino (2006)
10.1002/(SICI)1096-987X(199803)19:4%3C377::AID-JCC1%3E3.0.CO;2-P
Comparison of methods for deriving atomic charges from the electrostatic potential and moments
Emma Sigfridsson (1998)
Interpretation of Protein Titration Curves
C. Tanford (1972)
J. Comp. Chem
10.1016/0014-5793(93)80291-2
pH dependence of light‐induced proton release by bacteriorhodopsin
M. Kono (1993)
10.1093/nar/28.1.235
The Protein Data Bank
H. Berman (2000)
An object-oriented programming suite electrostatic effects in biological molecules. An experience report on the MEAD project
D Bashford (1997)
10.1021/BI00496A010
pKa's of ionizable groups in proteins: atomic detail from a continuum electrostatic model.
D. Bashford (1990)
10.1073/PNAS.0408930102
Molecular dynamics and protein function.
M. Karplus (2005)
10.1186/1758-2946-3-33
Open Babel: An open chemical toolbox
Noel M. O'Boyle (2011)
10.1016/S0006-3495(96)79591-7
Titration of aspartate-85 in bacteriorhodopsin: what it says about chromophore isomerization and proton release.
S. Balashov (1996)
10.1016/S0006-3495(02)73940-4
Combining conformational flexibility and continuum electrostatics for calculating pK(a)s in proteins.
R. Georgescu (2002)
Theory of Protein Titration Curves
C. Tanford (1957)
10.1089/cmb.2007.0144
Analysis of Basic Clustering Algorithms for Numerical Estimation of Statistical Averages in Biomolecules
Ramu Anandakrishnan (2008)
10.1016/S0022-2836(03)00903-3
Proton affinity changes driving unidirectional proton transport in the bacteriorhodopsin photocycle.
A. Onufriev (2003)
10.1002/prot.22470
Molecular determinants of the pKa values of Asp and Glu residues in staphylococcal nuclease
Carlos A Castañeda (2009)
10.1016/J.STR.2005.11.014
Molecular dynamics simulations of the complete satellite tobacco mosaic virus.
Peter L. Freddolino (2006)
10.1073/PNAS.88.13.5804
Protonation of interacting residues in a protein by a Monte Carlo method: application to lysozyme and the photosynthetic reaction center of Rhodobacter sphaeroides.
P. Beroza (1991)
10.1002/BIP.360320802
Electrostatic forces in two lysozymes: Calculations and measurements of histidine pKa values
T. Takahashi (1992)
On the Calculation of pKa’s
Yang (1993)
10.1002/prot.1053
Optimizing the hydrogen‐bond network in Poisson–Boltzmann equation‐based pKa calculations
J. E. Nielsen (2001)
10.1021/JP963412W
Consistent Calculations of pKa's of Ionizable Residues in Proteins: Semi-microscopic and Microscopic Approaches
Y. Sham (1997)
10.1002/(SICI)1096-987X(199908)20:11%3C1091::AID-JCC1%3E3.0.CO;2-3
Multiple-site ligand binding to flexible macromolecules: Separation of global and local conformational change and an iterative mobile clustering approach
V. Spassov (1999)
10.1007/3-540-31618-3
New algorithms for macromolecular simulation
B. Leimkuhler (2006)
10.1073/pnas.1004213107
Charges in the hydrophobic interior of proteins
Daniel G. Isom (2010)
10.1007/3-540-63827-X
Scientific Computing in Object-Oriented Parallel Environments
Y. Ishikawa (1997)
10.1002/PROT.340150304
On the calculation of pKas in proteins
A. Yang (1993)
On the Calculation of p Ka ’ s in Proteins
A.-S. Yang (1993)
10.1146/ANNUREV.BIOPHYS.30.1.211
Biomolecular simulations: recent developments in force fields, simulations of enzyme catalysis, protein-ligand, protein-protein, and protein-nucleic acid noncovalent interactions.
W. Wang (2001)
Protonation of interacting residues in a protein by Monte Carlo method
P. Beroza (1991)
10.1002/jcc.20139
Constant pH molecular dynamics in generalized Born implicit solvent
J. Mongan (2004)
10.1021/J100785A001
van der Waals Volumes and Radii
A. Bondi (1964)
Molecular dynamics simulations of the Complete Satellite Tobacco
P. L. Freddolino (2006)
10.1002/jcc.21222
MCCE2: Improving protein pKa calculations with extensive side chain rotamer sampling
Y. Song (2009)
10.1007/s002490050236
Electrostatic models for computing protonation and redox equilibria in proteins
G. Ullmann (1999)
10.1006/JMBI.1998.2401
Asparagine and glutamine: using hydrogen atom contacts in the choice of side-chain amide orientation.
J. Word (1999)
10.1002/prot.1106
What are the dielectric “constants” of proteins and how to validate electrostatic models?
C. N. Schutz (2001)
10.1017/S0033583510000284
Biomolecularmodeling and simulation: a field coming of age.
T. Schlick (2011)
J. Comput. Chem
10.1002/(SICI)1096-987X(199908)20:11<1091::AID-JCC1>3.0.CO;2-3
Multiple‐site ligand binding to flexible macromolecules: Separation of global and local conformational change and an iterative mobile clustering approach
V. Spassov (1999)
10.1093/nar/gki464
H++: a server for estimating pKas and adding missing hydrogens to macromolecules
J. C. Gordon (2005)
10.1007/978-94-011-2718-9_10
Electrostatic calculations of the pKa values of ionizable groups in bacteriorhodopsin.
D. Bashford (1992)
10.1093/nar/gni073
Analysis of scanning force microscopy images of protein-induced DNA bending using simulations
R. T. Dame (2005)
10.1002/prot.20922
A simple clustering algorithm can be accurate enough for use in calculations of pKs in macromolecules
J. Myers (2006)
10.1110/ps.073397708
A buried lysine that titrates with a normal pKa: Role of conformational flexibility at the protein–water interface as a determinant of pKavalues
Michael J. Harms (2008)
10.1021/BI00761A029
Interpretation of protein titration curves. Application to lysozyme.
C. Tanford (1972)
10.1006/JMBI.2001.4902
pK(a) Calculations suggest storage of an excess proton in a hydrogen-bonded water network in bacteriorhodopsin.
V. Spassov (2001)



This paper is referenced by
10.3390/molecules19021828
Theoretical Study on the Allosteric Regulation of an Oligomeric Protease from Pyrococcus horikoshii by Cl− Ion
Dongling Zhan (2014)
10.1016/j.bioorg.2018.09.003
Inhibitory properties of aromatic thiosemicarbazones on mushroom tyrosinase: Synthesis, kinetic studies, molecular docking and effectiveness in melanogenesis inhibition.
K. Hałdys (2018)
10.1080/07391102.2018.1517610
Comparative in silico study of the differences in the structure and ligand interaction properties of three alpha-expansin proteins from Fragaria chiloensis fruit
Felipe Valenzuela-Riffo (2019)
10.1021/am500167c
Mechanism of graphene oxide as an enzyme inhibitor from molecular dynamics simulations.
X. Sun (2014)
10.1371/journal.pone.0198990
Modulating D-amino acid oxidase (DAAO) substrate specificity through facilitated solvent access
Kalyanasundaram Subramanian (2018)
10.1371/journal.pcbi.1005787
The ins and outs of vanillyl alcohol oxidase: Identification of ligand migration paths
Gudrun Gygli (2017)
10.1016/j.envpol.2019.02.058
Computational insights on agonist and antagonist mechanisms of estrogen receptor α induced by bisphenol A analogues.
Huiming Cao (2019)
10.1016/j.bbagen.2018.11.010
Mechanistic insights into metal ions transit through threefold ferritin channel.
B. Chandramouli (2019)
10.3390/toxins11110625
The Sequence and a Three-Dimensional Structural Analysis Reveal Substrate Specificity among Snake Venom Phosphodiesterases
A. Ullah (2019)
10.1093/glycob/cwv048
Cello-oligomer-binding dynamics and directionality in family 4 carbohydrate-binding modules.
Abhishek A. Kognole (2015)
10.1063/1.4913961
Parallel scalability of Hartree-Fock calculations.
E. Chow (2015)
10.1074/jbc.RA117.000313
The partial dissociation of MHC class I–bound peptides exposes their N terminus to trimming by endoplasmic reticulum aminopeptidase 1
A. Papakyriakou (2018)
10.1016/j.saa.2020.118133
Concerted motion of structure and active site charge is required for tyrosine aminotransferase activity in Leishmania parasite.
Santanu Sasidharan (2020)
10.1016/j.jmgm.2017.04.009
Study of the mechanism of protonated histidine-induced conformational changes in the Zika virus dimeric envelope protein using accelerated molecular dynamic simulations.
J. Sun (2017)
University of Dundee On the ion coupling mechanism of the MATE transporter ClbM Krah,
A. Krah (2019)
10.1038/s41598-020-72243-9
Thyroxine binding to type III iodothyronine deiodinase
C. A. Bayse (2020)
10.1021/acs.jpcb.7b03966
Distinct Protein Hydration Water Species Defined by Spatially Resolved Spectra of Intermolecular Vibrations
V. Pattni (2017)
10.1038/srep29249
Conformational stability of digestion-resistant peptides of peanut conglutins reveals the molecular basis of their allergenicity
D. Apostolović (2016)
10.1080/07391102.2017.1377636
A comprehensive analysis of the computed tautomer fractions of the imidazole ring of histidines in Loligo vulgaris
Y. Vorobjev (2018)
10.1371/journal.pone.0051352
A Partition Function Approximation Using Elementary Symmetric Functions
Ramu Anandakrishnan (2012)
Consistent approach for calculating protein pKa's using Poisson-Boltzmann Model
Han Wool Yoon (2013)
10.21236/ada601589
Hydrogen Production from Water by Photosynthesis System I for Use as Fuel in Energy Conversion Devices (a.k.a. Understanding Photosystem I as a Biomolecular Reactor for Energy Conversion)
Cynthia A. Lundgren (2014)
New insights into principles of scaffolds design for bone application
Hongji Yan (2016)
10.19261/CJM.2015.10(1).10
An Investigation of the Protonation States of Human Lactoferrin Iron-Binding Protein
Lilia Anghel (2015)
10.3390/ijms20205142
Exploring the Binding Mechanism and Dynamics of EndoMS/NucS to Mismatched dsDNA
Yan-jun Zhang (2019)
10.1016/j.chemosphere.2019.125796
A novel concept for the biodegradation mechanism of dianionic catechol with homoprotocatechuate 2,3-dioxygenase: A non-proton-assisted process.
Ningyu Tu (2019)
Improving of the accuracy and efficiency of implicit solvent models in Biomolecular Modeling
Aguilar Huacan (2014)
10.1002/jcb.27543
Computational insights into pH‐dependence of structure and dynamics of pyrazinamidase: A comparison of wild type and mutants
Reza Esmaeeli (2018)
10.1039/c9ra05763c
In vitro and in silico determination of glutaminyl cyclase inhibitors
P. Tran (2019)
10.1016/j.jmgm.2016.12.011
Accuracy comparison of several common implicit solvent models and their implementations in the context of protein-ligand binding.
E. Katkova (2017)
10.1101/252817
Cooperative Cobinding of Synthetic and Natural Ligands to the Nuclear Receptor PPARγ
Jinsai Shang (2018)
10.1021/acs.biochem.6b00461
Insight into the Mechanism of Hydrolysis of Meropenem by OXA-23 Serine-β-lactamase Gained by Quantum Mechanics/Molecular Mechanics Calculations.
Jacopo Sgrignani (2016)
See more
Semantic Scholar Logo Some data provided by SemanticScholar