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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
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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
The Amber biomolecular simulation programs
D. A. Case (2005)
Intrinsic pKas of ionizable residues in proteins: An explicit solvent calculation for lysozyme
G. S. Del Buono (1994)
Molecular dynamics simulations of biomolecules
M. Karplus (2002)
Interpretation of Protein Titration
C. Tanford (1972)
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)
A novel view of pH titration in biomolecules.
A. Onufriev (2001)
Improving the Continuum Dielectric Approach to Calculating pKas of Ionizable Groups in Proteins
E. Demchuk (1996)
Theory of Protein Titration Curves. I. General Equations for Impenetrable Spheres
C. Tanford (1957)
Chemically accurate protein structures: Validation of protein NMR structures by comparison of measured and predicted pKa values
N. Powers (2006)
A fast and accurate computational approach to protein ionization
V. Spassov (2008)
Molecular simulations of protein dynamics: new windows on mechanisms in biology
G. Dodson (2008)
Prediction of pH-dependent properties of proteins.
J. Antosiewicz (1994)
Constant‐pH molecular dynamics using continuous titration coordinates
M. Lee (2004)
A summary of the measured pK values of the ionizable groups in folded proteins
G. Grimsley (2009)
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)
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
pH dependence of light‐induced proton release by bacteriorhodopsin
M. Kono (1993)
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)
pKa's of ionizable groups in proteins: atomic detail from a continuum electrostatic model.
D. Bashford (1990)
Molecular dynamics and protein function.
M. Karplus (2005)
Open Babel: An open chemical toolbox
Noel M. O'Boyle (2011)
Titration of aspartate-85 in bacteriorhodopsin: what it says about chromophore isomerization and proton release.
S. Balashov (1996)
Combining conformational flexibility and continuum electrostatics for calculating pK(a)s in proteins.
R. Georgescu (2002)
Theory of Protein Titration Curves
C. Tanford (1957)
Analysis of Basic Clustering Algorithms for Numerical Estimation of Statistical Averages in Biomolecules
Ramu Anandakrishnan (2008)
Proton affinity changes driving unidirectional proton transport in the bacteriorhodopsin photocycle.
A. Onufriev (2003)
Molecular determinants of the pKa values of Asp and Glu residues in staphylococcal nuclease
Carlos A Castañeda (2009)
Molecular dynamics simulations of the complete satellite tobacco mosaic virus.
Peter L. Freddolino (2006)
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)
Electrostatic forces in two lysozymes: Calculations and measurements of histidine pKa values
T. Takahashi (1992)
On the Calculation of pKa’s
Optimizing the hydrogen‐bond network in Poisson–Boltzmann equation‐based pKa calculations
J. E. Nielsen (2001)
Consistent Calculations of pKa's of Ionizable Residues in Proteins: Semi-microscopic and Microscopic Approaches
Y. Sham (1997)
Multiple-site ligand binding to flexible macromolecules: Separation of global and local conformational change and an iterative mobile clustering approach
V. Spassov (1999)
New algorithms for macromolecular simulation
B. Leimkuhler (2006)
Charges in the hydrophobic interior of proteins
Daniel G. Isom (2010)
Scientific Computing in Object-Oriented Parallel Environments
Y. Ishikawa (1997)
On the calculation of pKas in proteins
A. Yang (1993)
On the Calculation of p Ka ’ s in Proteins
A.-S. Yang (1993)
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)
Constant pH molecular dynamics in generalized Born implicit solvent
J. Mongan (2004)
van der Waals Volumes and Radii
A. Bondi (1964)
Molecular dynamics simulations of the Complete Satellite Tobacco
P. L. Freddolino (2006)
MCCE2: Improving protein pKa calculations with extensive side chain rotamer sampling
Y. Song (2009)
Electrostatic models for computing protonation and redox equilibria in proteins
G. Ullmann (1999)
Asparagine and glutamine: using hydrogen atom contacts in the choice of side-chain amide orientation.
J. Word (1999)
What are the dielectric “constants” of proteins and how to validate electrostatic models?
C. N. Schutz (2001)
Biomolecularmodeling and simulation: a field coming of age.
T. Schlick (2011)
J. Comput. Chem
Multiple‐site ligand binding to flexible macromolecules: Separation of global and local conformational change and an iterative mobile clustering approach
V. Spassov (1999)
H++: a server for estimating pKas and adding missing hydrogens to macromolecules
J. C. Gordon (2005)
Electrostatic calculations of the pKa values of ionizable groups in bacteriorhodopsin.
D. Bashford (1992)
Analysis of scanning force microscopy images of protein-induced DNA bending using simulations
R. T. Dame (2005)
A simple clustering algorithm can be accurate enough for use in calculations of pKs in macromolecules
J. Myers (2006)
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)
Interpretation of protein titration curves. Application to lysozyme.
C. Tanford (1972)
pK(a) Calculations suggest storage of an excess proton in a hydrogen-bonded water network in bacteriorhodopsin.
V. Spassov (2001)
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Dongling Zhan (2014)
Inhibitory properties of aromatic thiosemicarbazones on mushroom tyrosinase: Synthesis, kinetic studies, molecular docking and effectiveness in melanogenesis inhibition.
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Computational insights on agonist and antagonist mechanisms of estrogen receptor α induced by bisphenol A analogues.
Huiming Cao (2019)
Mechanistic insights into metal ions transit through threefold ferritin channel.
B. Chandramouli (2019)
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A. Ullah (2019)
Cello-oligomer-binding dynamics and directionality in family 4 carbohydrate-binding modules.
Abhishek A. Kognole (2015)
Parallel scalability of Hartree-Fock calculations.
E. Chow (2015)
The partial dissociation of MHC class I–bound peptides exposes their N terminus to trimming by endoplasmic reticulum aminopeptidase 1
A. Papakyriakou (2018)
Concerted motion of structure and active site charge is required for tyrosine aminotransferase activity in Leishmania parasite.
Santanu Sasidharan (2020)
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)
Thyroxine binding to type III iodothyronine deiodinase
C. A. Bayse (2020)
Distinct Protein Hydration Water Species Defined by Spatially Resolved Spectra of Intermolecular Vibrations
V. Pattni (2017)
Conformational stability of digestion-resistant peptides of peanut conglutins reveals the molecular basis of their allergenicity
D. Apostolović (2016)
A comprehensive analysis of the computed tautomer fractions of the imidazole ring of histidines in Loligo vulgaris
Y. Vorobjev (2018)
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)
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)
An Investigation of the Protonation States of Human Lactoferrin Iron-Binding Protein
Lilia Anghel (2015)
Exploring the Binding Mechanism and Dynamics of EndoMS/NucS to Mismatched dsDNA
Yan-jun Zhang (2019)
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)
Computational insights into pH‐dependence of structure and dynamics of pyrazinamidase: A comparison of wild type and mutants
Reza Esmaeeli (2018)
In vitro and in silico determination of glutaminyl cyclase inhibitors
P. Tran (2019)
Accuracy comparison of several common implicit solvent models and their implementations in the context of protein-ligand binding.
E. Katkova (2017)
Cooperative Cobinding of Synthetic and Natural Ligands to the Nuclear Receptor PPARγ
Jinsai Shang (2018)
Insight into the Mechanism of Hydrolysis of Meropenem by OXA-23 Serine-β-lactamase Gained by Quantum Mechanics/Molecular Mechanics Calculations.
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