tCONCOORD‐GUI: Visually supported conformational sampling of bioactive molecules

Seeliger, Daniel; Groot, Bert L. de

doi:10.1002/jcc.21127

Cited by 38 publications

(34 citation statements)

References 18 publications

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“…The tCONCOORD ensembles also sample structures not found in the ensemble of crystal structures, particularly when using the open conformation as input. This tendency of tCONCOORD to produce ensembles with too much structural variability was also noted by the authors (Seeliger and de Groot, 2009). …”

Section: Resultssupporting

confidence: 72%

Predicting Protein Dynamics and Allostery Using Multi-Protein Atomic Distance Constraints

2017

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SummaryThe related concepts of protein dynamics, conformational ensembles and allostery are often difficult to study with molecular dynamics (MD) due to the timescales involved. We present ExProSE (Exploration of Protein Structural Ensembles), a distance geometry-based method that generates an ensemble of protein structures from two input structures. ExProSE provides a unified framework for the exploration of protein structure and dynamics in a fast and accessible way. Using a dataset of apo/holo pairs it is shown that existing coarse-grained methods often cannot span large conformational changes. For T4-lysozyme, ExProSE is able to generate ensembles that are more native-like than tCONCOORD and NMSim, and comparable with targeted MD. By adding additional constraints representing potential modulators, ExProSE can predict allosteric sites. ExProSE ranks an allosteric pocket first or second for 27 out of 58 allosteric proteins, which is similar and complementary to existing methods. The ExProSE source code is freely available.

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Section: Resultssupporting

confidence: 72%

Predicting Protein Dynamics and Allostery Using Multi-Protein Atomic Distance Constraints

2017

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“…3b, blue/broad regions indicate larger conformational changes upon complex formation compared to red/narrow regions). tCONCOORD [24] conformational space analysis (see Supplementary Methods) reveals that unbound AbbA has the propensity to sample a larger conformational space within its first 30 residues compared to the rest of the protein (Fig. 3c).…”

Section: Resultsmentioning

confidence: 99%

A DNA Mimic: The Structure and Mechanism of Action for the Anti-Repressor Protein AbbA

Tucker

Bobay

Banse

et al. 2014

Journal of Molecular Biology

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Bacteria respond to adverse environmental conditions by switching on the expression of large numbers of genes that enable them to adapt to unfavorable circumstances. In Bacillus subtilis, many adaptive genes are under the negative control of the global transition state regulator, the repressor protein AbrB. Stressful conditions lead to the de-repression of genes under AbrB control. Contributing to this de-repression is AbbA, an anti-repressor that binds to and blocks AbrB from binding to DNA. Here, we have determined the NMR structure of the functional AbbA dimer, confirmed that it binds to the N-terminal DNA-binding domain of AbrB, and have provided an initial description for the interaction using computational docking procedures. Interestingly, we show that AbbA has structural and surface characteristics that closely mimic the DNA phosphate backbone, enabling it to readily carry out its physiological function.

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“…All crystal water molecules were retained. Two short loops missing in the γ-subunit (62-66 and 97-100) were modeled using tCONCOORD (28). The same software was used to form disulfide bonds between the rotor and stator either in the center of the α 3 β 3 -cylinder (the cross-link designated as CL1 in Fig.…”

Section: Methodsmentioning

confidence: 99%

Torsional elasticity and energetics of F ₁ -ATPase

Czub

Grubmüller

2011

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

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F o F 1 -ATPase is a rotary motor protein synthesizing ATP from ADP driven by a cross-membrane proton gradient. The proton flow through the membrane-embedded F o generates the rotary torque that drives the rotation of the asymmetric shaft of F 1 . Mechanical energy of the rotating shaft is used by the F 1 catalytic subunit to synthesize ATP. It was suggested that elastic power transmission with transient storage of energy in some compliant part of the shaft is required for the observed high turnover rate. We used atomistic simulations to study the spatial distribution and structural determinants of the F 1 torsional elasticity at the molecular level and to comprehensively characterize the elastic properties of F 1 -ATPase. Our fluctuation analysis revealed an unexpected heterogeneity of the F 1 shaft elasticity. Further, we found that the measured overall torsional moduli of the shaft arise from two distinct contributions, the intrinsic elasticity and the effective potential imposed on the shaft by the catalytic subunit. Separation of these two contributions provided a quantitative description of the coupling between the rotor and the catalytic subunit. This description enabled us to propose a minimal quantitative model of the F 1 energetics along the rotary degrees of freedom near the resting state observed in the crystal structures. As opposed to the usually employed models where the motor mechanical progression is described by a single angular variable, our multidimensional treatment incorporates the spatially inhomogeneous nature of the shaft and its interactions with the stator and offers new insight into the mechanoenzymatics of F 1 -ATPase. molecular dynamics | molecular motor | ATP synthase

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tCONCOORD‐GUI: Visually supported conformational sampling of bioactive molecules

Cited by 38 publications

References 18 publications

Predicting Protein Dynamics and Allostery Using Multi-Protein Atomic Distance Constraints

Predicting Protein Dynamics and Allostery Using Multi-Protein Atomic Distance Constraints

A DNA Mimic: The Structure and Mechanism of Action for the Anti-Repressor Protein AbbA

Torsional elasticity and energetics of F ₁ -ATPase

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tCONCOORD‐GUI: Visually supported conformational sampling of bioactive molecules

Cited by 38 publications

References 18 publications

Predicting Protein Dynamics and Allostery Using Multi-Protein Atomic Distance Constraints

Predicting Protein Dynamics and Allostery Using Multi-Protein Atomic Distance Constraints

A DNA Mimic: The Structure and Mechanism of Action for the Anti-Repressor Protein AbbA

Torsional elasticity and energetics of F 1 -ATPase

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Torsional elasticity and energetics of F ₁ -ATPase