SAXS-Guided Metadynamics

Kimanius, Dari; Pettersson, Ingrid; Schluckebier, G.; Lindahl, Erik; Andersson, Magnus

doi:10.1021/acs.jctc.5b00299

Cited by 39 publications

(24 citation statements)

References 58 publications

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“…This has driven a dramatic increase in the variety and complexity of CVs employed, well beyond traditional distances, angles and root mean square deviations (RMSD) with respect to known configurations, and thus making a service for all other methods based on CVs. For example, for biological systems, the effort resulted in the development of CVs to follow paths in conformational space [58], CVs specific for proteins [59,60] or nucleic acids [61], CVs for interfacial water molecules [62], CVs for experimental observables [63][64][65], for shapes [66], and more (cf. the manual of the PLUMED code for more examples [67,68]).…”

Section: The Problem Of Thermodynamics: Learning From Kineticsmentioning

confidence: 99%

Advanced simulation techniques for the thermodynamic and kinetic characterization of biological systems

Camilloni

Pietrucci

2018

Advances in Physics: X

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This review discusses successful strategies and key open problems in the kinetic and thermodynamic characterization of complex biomolecular systems by computer simulations. The main focus is on established techniques and emerging trends in the fields of enhanced sampling and of kinetic models, as applied to biological problems ranging from protein folding and conformational dynamics to protein-protein and proteinligand interaction. We address especially the following questions: How to choose a computational approach suited to a particular problem? What are the strengths and limitations of alternative approaches? What is the current accuracy of thermodynamic and kinetic predictions? What are today's open challenges and promising development directions? Towards the aim of accurately reproducing and interpreting experimental results, we briefly discuss hybrid approaches that combine together theoretical and experimental information.

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Section: The Problem Of Thermodynamics: Learning From Kineticsmentioning

confidence: 99%

Advanced simulation techniques for the thermodynamic and kinetic characterization of biological systems

Camilloni

Pietrucci

2018

Advances in Physics: X

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“…applying the metainference bias only at every few time steps (Ferrarotti et al, 2015). This can be useful to further speed up the simulations and is fully justified in the case of SAXS data since the temporal fluctuations of this variable are slower than the ones in atomistic coordinates (Kimanius et al, 2015).…”

Section: Hybrid All-atom/coarse-grain Saxs Calculation and Plumed-isdmentioning

confidence: 99%

Martini bead form factors for nucleic-acids and their application in the refinement of protein/nucleic-acid complexes against SAXS data

Paissoni

Jussupow

Camilloni

2018

Preprint

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Small-angle X-ray scattering (SAXS) use in combination with molecular dynamics simulation is hampered by its heavy computational cost. The calculation of SAXS from atomic structures can be speed up by using a coarse grain representation of the structure. Here following the work of Niebling, et al. (J. Appl. Cryst., (2014), 47, 1190 we derived the Martini beads form factors for nucleic acids and we implemented them, together with those previously determined for proteins, in the publicly available PLUMED library. We also implemented a hybrid multi-resolution strategy to perform SAXS restrained simulations at atomic resolution by calculating on-the-fly the virtual position of the Martini beads and using them for the calculation of SAXS. The accuracy and efficiency of the method is demonstrated by refining the structure of two protein/nucleic acid complexes. Instrumental for this result is the use of metainference that allows considering and alleviating the approximations at play in our SAXS calculation.

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“…The missing high-resolution information from scattering can be readily furnished via other sources including crystallography (Grant et al, 2011;Putnam et al, 2007) and NMR (Carlomagno, 2014;Grishaev et al, 2005;Madl et al, 2011;Rossi et al, 2015). Such combination enables the isolation of complex structures where SAXS can be used as a guide in rigid-body docking (Jiménez-García et al, 2015;Petoukhov and Svergun, 2005;Schindler et al, 2016;Schneidman-Duhovny et al, 2016;Xia et al, 2015), elastic perturbations (Gorba et al, 2008;Tekpinar, 2011), atomistic simulations (Björling et al, 2015;Chen and Hub, 2015a;Kimanius et al, 2015), or trivially as post-hoc removal of incompatible structural models (Hennig et al, 2013;Karaca and Bonvin, 2013). Moreover, mixtures of monodisperse species can be decomposed (Bernadó et al, 2007;Schneidman-Duhovny et al, 2016) when either the relative populations or the component scattering are already known.…”

Section: Applications In Structural Biologymentioning

confidence: 99%

The role of small-angle scattering in structure-based screening applications

Chen

Hennig

2018

Biophys Rev

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In many biomolecular interactions, changes in the assembly states and structural conformations of participants can act as a complementary reporter of binding to functional and thermodynamic assays. This structural information is captured by a number of structural biology and biophysical techniques that are viable either as primary screens in small-scale applications or as secondary screens to complement higher throughput methods. In particular, small-angle X-ray scattering (SAXS) reports the average distance distribution between all atoms after orientational averaging. Such information is important when e.g. investigating conformational changes involved in inhibitory and regulatory mechanisms where binding events do not necessarily cause functional changes.Thus, we summarise here the current and prospective capabilities of SAXS-based screening in the context of other methods that yield structural information. Broad guidelines are also provided to assist readers in preparing screening protocols that are tailored to available X-ray sources.

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SAXS-Guided Metadynamics

Cited by 39 publications

References 58 publications

Advanced simulation techniques for the thermodynamic and kinetic characterization of biological systems

Advanced simulation techniques for the thermodynamic and kinetic characterization of biological systems

Martini bead form factors for nucleic-acids and their application in the refinement of protein/nucleic-acid complexes against SAXS data

The role of small-angle scattering in structure-based screening applications

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