A statistical approach to the prediction of p<i>K</i><sub>a</sub> values in proteins

He, Yunlong; Xu, Jialin; Pan, Xian-Ming

doi:10.1002/prot.21478

Cited by 23 publications

(27 citation statements)

References 61 publications

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“…PROPKA data were obtained using the publicly available web interface (http://propka.ki.ku.dk). Several other methods for the prediction of p K a values are available, e.g., MCCE (25, 26), MEAD (27), and PKAcal (28). However, PROPKA performed well in several benchmarking studies (e.g., refs (23), (24), and (29)) and was therefore our method of choice.…”

Section: Methodsmentioning

confidence: 99%

DNA Recognition by the DNA Primase of Bacteriophage T7: A Structure−Function Study of the Zinc-Binding Domain

et al. 2009

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Synthesis of oligoribonucleotide primers for lagging-strand DNA synthesis in the DNA replication system of bacteriophage T7 is catalyzed by the primase domain of the gene 4 helicase-primase. The primase consists of a zinc-binding domain (ZBD) and an RNA polymerase (RPD) domain. The ZBD is responsible for recognition of a specific sequence in the ssDNA template whereas catalytic activity resides in the RPD. The ZBD contains a zinc ion coordinated with four cysteine residues. We have examined the ligation state of the zinc ion by X-ray absorption spectroscopy and biochemical analysis of genetically altered primases. The ZBD of primase engaged in catalysis exhibits considerable asymmetry in coordination to zinc, as evidenced by a gradual increase in electron density of the zinc together with elongation of the zinc–sulfur bonds. Both wild-type primase and primase reconstituted from purified ZBD and RPD have a similar electronic change in the level of the zinc ion as well as the configuration of the ZBD. Single amino acid replacements in the ZBD (H33A and C36S) result in the loss of both zinc binding and its structural integrity. Thus the zinc in the ZBD may act as a charge modulation indicator for the surrounding sulfur atoms necessary for recognition of specific DNA sequences.

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Section: Methodsmentioning

confidence: 99%

DNA Recognition by the DNA Primase of Bacteriophage T7: A Structure−Function Study of the Zinc-Binding Domain

et al. 2009

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“…Significant improvements over continuum electrostatics (and more in general molecular mechanics) methods have been achieved by parametrization of interactions [49,50,66-69]. …”

Section: Methodsmentioning

confidence: 99%

Bluues: a program for the analysis of the electrostatic properties of proteins based on generalized Born radii

et al. 2012

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BackgroundThe Poisson-Boltzmann (PB) equation and its linear approximation have been widely used to describe biomolecular electrostatics. Generalized Born (GB) models offer a convenient computational approximation for the more fundamental approach based on the Poisson-Boltzmann equation, and allows estimation of pairwise contributions to electrostatic effects in the molecular context.ResultsWe have implemented in a single program most common analyses of the electrostatic properties of proteins. The program first computes generalized Born radii, via a surface integral and then it uses generalized Born radii (using a finite radius test particle) to perform electrostic analyses. In particular the ouput of the program entails, depending on user's requirement:1) the generalized Born radius of each atom;2) the electrostatic solvation free energy;3) the electrostatic forces on each atom (currently in a dvelopmental stage);4) the pH-dependent properties (total charge and pH-dependent free energy of folding in the pH range -2 to 18;5) the pKa of all ionizable groups;6) the electrostatic potential at the surface of the molecule;7) the electrostatic potential in a volume surrounding the molecule;ConclusionsAlthough at the expense of limited flexibility the program provides most common analyses with requirement of a single input file in PQR format. The results obtained are comparable to those obtained using state-of-the-art Poisson-Boltzmann solvers. A Linux executable with example input and output files is provided as supplementary material.

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“…Multiple protonation states of each receptor were generated, depending on the predicted p K a values for each asparate, cystine, glutamate, histidine, lysine, or tyrosine whose calculated p K a was between 5 and 9 51. Only residues within a radius of 5 Å from any ligand were considered.…”

Section: Methodsmentioning

confidence: 99%

Estimating binding affinities by docking/scoring methods using variable protonation states

2010

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To investigate the effects of multiple protonation states on protein-ligand recognition, we generated alternative protonation states for selected titratable groups of ligands and receptors. The selection of states was based on the predicted pK(a) of the unbound receptor and ligand and the proximity of titratable groups of the receptor to the binding site. Various ligand tautomer states were also considered. An independent docking calculation was run for each state. Several protocols were examined: using an ensemble of all generated states of ligand and receptor, using only the most probable state of the unbound ligand/receptor, and using only the state giving the most favorable docking score. The accuracies of these approaches were compared, using a set of 176 protein-ligand complexes (15 receptors) for which crystal structures and measured binding affinities are available. The best agreement with experiment was obtained when ligand poses from experimental crystal structures were used. For 9 of 15 receptors, using an ensemble of all generated protonation states of the ligand and receptor gave the best correlation between calculated and measured affinities.

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A statistical approach to the prediction of pK_a values in proteins

Cited by 23 publications

References 61 publications

DNA Recognition by the DNA Primase of Bacteriophage T7: A Structure−Function Study of the Zinc-Binding Domain

DNA Recognition by the DNA Primase of Bacteriophage T7: A Structure−Function Study of the Zinc-Binding Domain

Bluues: a program for the analysis of the electrostatic properties of proteins based on generalized Born radii

Estimating binding affinities by docking/scoring methods using variable protonation states

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A statistical approach to the prediction of pKa values in proteins

Cited by 23 publications

References 61 publications

DNA Recognition by the DNA Primase of Bacteriophage T7: A Structure−Function Study of the Zinc-Binding Domain

DNA Recognition by the DNA Primase of Bacteriophage T7: A Structure−Function Study of the Zinc-Binding Domain

Bluues: a program for the analysis of the electrostatic properties of proteins based on generalized Born radii

Estimating binding affinities by docking/scoring methods using variable protonation states

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A statistical approach to the prediction of pK_a values in proteins