PDB2PQR: expanding and upgrading automated preparation of biomolecular structures for molecular simulations

Dolinsky, Todd J.; Czodrowski, Paul; Li, Hui; Nielsen, Jens Erik; Jensen, Jan H.; Klebe, G.; Baker, Nathan A.

doi:10.1093/nar/gkm276

Cited by 1,745 publications

(1,510 citation statements)

References 27 publications

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“…Calculation of all electrostatic potential surfaces were performed using the APBS (Adaptive Poisson-Boltzmann Solver) software package (45). The coordinates of the 3BZ1-1 PSII and the 1HRC cyt c structures were modified using PDB2PQR (46) to include hydrogen and partial charges, followed by surface calculation and visualization using the APBS plugin in Pymol (47). All electrostatic potentials are presented at AE15 kT∕e.…”

Section: Methodsmentioning

confidence: 99%

Engineering of an alternative electron transfer path in photosystem II

Larom

Salama

Schuster

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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The initial steps of oxygenic photosynthetic electron transfer occur within photosystem II, an intricate pigment/protein transmembrane complex. Light-driven electron transfer occurs within a multistep pathway that is efficiently insulated from competing electron transfer pathways. The heart of the electron transfer system, composed of six linearly coupled redox active cofactors that enable electron transfer from water to the secondary quinone acceptor Q B , is mainly embedded within two proteins called D1 and D2. We have identified a site in silico, poised in the vicinity of the Q A intermediate quinone acceptor, which could serve as a potential binding site for redox active proteins. Here we show that modification of Lysine 238 of the D1 protein to glutamic acid (Glu) in the cyanobacterium Synechocystis sp. PCC 6803, results in a strain that grows photautotrophically. The Glu thylakoid membranes are able to perform light-dependent reduction of exogenous cytochrome c with water as the electron donor. Cytochrome c photoreduction by the Glu mutant was also shown to significantly protect the D1 protein from photodamage when isolated thylakoid membranes were illuminated. We have therefore engineered a novel electron transfer pathway from water to a soluble protein electron carrier without harming the normal function of photosystem II. cyanobacteria | energy conversion | proinhibition | photosynthesis | protein engineering P hotosynthesis is the major source of useful chemical energy in the biosphere. All photosynthetic processes require efficient electron transfer (ET) pathways that are utilized for proton gradient formation (to be used for the production of ATP) and/or accumulation of reducing equivalents (1, 2). Light energy, absorbed by light-harvesting antenna complexes, is transferred to photochemical reaction centers (RC), initiating charge separation in specific chlorophyll molecules bound to the RC proteins. Following charge separation, electrons are transferred sequentially to a series of acceptor molecules, each with a redox potential determined by its immediate environment (3, 4). The source of electron replenishment differs according to the reaction center type. For instance in purple non-sulfur bacteria, electrons are cycled back to the oxidized reaction center by a soluble cytochrome c (cyt c) type protein (5, 6). Oxygenic photosynthetic organisms (cyanobacteria, red and green algae and plants) contain two photosystems: photosystem I (PSI) and photosystem II (PSII) that work linearly (1, 7), and the source of electrons is water. One common facet of all ET pathways is the requirement for insulation of the redox active cofactors from potentially reducing/oxidizing molecules within the RC or in the surrounding media. Insulation provides the system with maximal ET rates and efficiencies and also prevents damage to the RC.PSII has a redox potential of up to 1.2 V (8, 9), required to abstract electrons from water (Fig. 1A). The photoexcited P 680 reaction center chlorophyll a primary donor transfers electron...

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Section: Methodsmentioning

confidence: 99%

Engineering of an alternative electron transfer path in photosystem II

Larom

Salama

Schuster

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…All calculations were carried out at 298.15 K with a solvent dielectric constant of 78.54 and a protein dielectric constant of 20. pKa calculations were performed on the protein structure only, taken from the last frame of a molecular dynamics (MD) simulation. Appropriate PQR files were generated with the aid of PDB2PQR version 1.4.0 [41,42], employing the CHARMM [43,44] parameterization.…”

Section: In Silico Pka Calculationsmentioning

confidence: 99%

Analytical characterization of NOTA-modified somatropins

Bracke

Wynendaele

D׳Hondt

et al. 2014

Journal of Pharmaceutical and Biomedical Analysis

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Highlights• NOTA-labeled somatropins were synthesized using different NOTA:protein ratios.• Direct LC-MS and CE-MS approaches indicated multiple substitution degrees.• Bottom-up approaches gave structural insights and information on the labeling yield.• Lys-70 (in silico calculated pKa of 8.3) is the NOTA-modification hotspot.• We report a synthesis procedure for the production of target-specific radiopharmaceuticals.

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“…All the atomic van der Waals radii are adopted from the CHARMM22 force field. 40 The partial charges for each atom in the protein are obtained by using the PDB2PQR software 46,47 and are accounted in ψ * . The solvent environment is represented by the dielectric continuum bulk environment, and the computational domain is a box which contains the protein.…”

Section: Cytochrome C551mentioning

confidence: 99%

Poisson–Boltzmann–Nernst–Planck model

Zheng

Wei

2011

The Journal of Chemical Physics

140

111

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The Poisson-Nernst-Planck (PNP) model is based on a mean-field approximation of ion interactions and continuum descriptions of concentration and electrostatic potential. It provides qualitative explanation and increasingly quantitative predictions of experimental measurements for the ion transport problems in many areas such as semiconductor devices, nanofluidic systems, and biological systems, despite many limitations. While the PNP model gives a good prediction of the ion transport phenomenon for chemical, physical, and biological systems, the number of equations to be solved and the number of diffusion coefficient profiles to be determined for the calculation directly depend on the number of ion species in the system, since each ion species corresponds to one Nernst-Planck equation and one position-dependent diffusion coefficient profile. In a complex system with multiple ion species, the PNP can be computationally expensive and parameter demanding, as experimental measurements of diffusion coefficient profiles are generally quite limited for most confined regions such as ion channels, nanostructures and nanopores. We propose an alternative model to reduce number of Nernst-Planck equations to be solved in complex chemical and biological systems with multiple ion species by substituting Nernst-Planck equations with Boltzmann distributions of ion concentrations. As such, we solve the coupled Poisson-Boltzmann and Nernst-Planck (PBNP) equations, instead of the PNP equations. The proposed PBNP equations are derived from a total energy functional by using the variational principle. We design a number of computational techniques, including the Dirichlet to Neumann mapping, the matched interface and boundary, and relaxation based iterative procedure, to ensure efficient solution of the proposed PBNP equations. Two protein molecules, cytochrome c551 and Gramicidin A, are employed to validate the proposed model under a wide range of bulk ion concentrations and external voltages. Extensive numerical experiments show that there is an excellent consistency between the results predicted from the present PBNP model and those obtained from the PNP model in terms of the electrostatic potentials, ion concentration profiles, and current-voltage (I-V) curves. The present PBNP model is further validated by a comparison with experimental measurements of I-V curves under various ion bulk concentrations. Numerical experiments indicate that the proposed PBNP model is more efficient than the original PNP model in terms of simulation time.

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PDB2PQR: expanding and upgrading automated preparation of biomolecular structures for molecular simulations

Cited by 1,745 publications

References 27 publications

Engineering of an alternative electron transfer path in photosystem II

Engineering of an alternative electron transfer path in photosystem II

Analytical characterization of NOTA-modified somatropins

Poisson–Boltzmann–Nernst–Planck model

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