Bioinformatics and molecular modeling in glycobiology

Frank, Martin; Schloissnig, Siegfried

doi:10.1007/s00018-010-0352-4

Cited by 78 publications

(53 citation statements)

References 243 publications

(225 reference statements)

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“…Many biophysical and computational techniques have been employed to gain knowledge about this from different perspectives. X-ray analysis [18], NMR spectroscopy [19], molecular modeling [20], mass spectrometry [21], surface plasmon resonance [22] and calorimetry [23], among others, have been used for determining key structural aspects for the formation of carbohydrate-protein complexes. …”

Section: Characterization Of Protein-carbohydrate Interactions By Nmrmentioning

confidence: 99%

Protein-Carbohydrate Interactions Studied by NMR: From Molecular Recognition to Drug Design

Fernández‐Alonso¹,

Díaz²,

Berbís³

et al. 2012

CPPS

121

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Diseases that result from infection are, in general, a consequence of specific interactions between a pathogenic organism and the cells. The study of host-pathogen interactions has provided insights for the design of drugs with therapeutic properties. One area that has proved to be promising for such studies is the constituted by carbohydrates which participate in biological processes of paramount importance. On the one hand, carbohydrates have shown to be information carriers with similar, if not higher, importance than traditionally considered carriers as amino acids and nucleic acids. On the other hand, the knowledge on molecular recognition of sugars by lectins and other carbohydrate-binding proteins has been employed for the development of new biomedical strategies. Biophysical techniques such as X-Ray crystallography and NMR spectroscopy lead currently the investigation on this field. In this review, a description of traditional and novel NMR methodologies employed in the study of sugar-protein interactions is briefly presented in combination with a palette of NMR-based studies related to biologically and/or pharmaceutically relevant applications.

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Section: Characterization Of Protein-carbohydrate Interactions By Nmrmentioning

confidence: 99%

Protein-Carbohydrate Interactions Studied by NMR: From Molecular Recognition to Drug Design

Fernández‐Alonso¹,

Díaz²,

Berbís³

et al. 2012

CPPS

121

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“…Currently, there are high-level carbohydrate force fields that are used for computer simulations (Fadda and Woods 2010). Several easy-touse Web-tools for modeling carbohydrate 3D structures also prompt investigation of MD simulations (Frank and Schloissnig 2010;Jo et al 2011).…”

Section: Molecular Dynamics Simulations Of N-glycansmentioning

confidence: 99%

Conformational flexibility of N-glycans in solution studied by REMD simulations

Nishima

Miyashita³

et al. 2012

Biophys Rev

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Protein-glycan recognition regulates a wide range of biological and pathogenic processes. Conformational diversity of glycans in solution is apparently incompatible with specific binding to their receptor proteins. One possibility is that among the different conformational states of a glycan, only one conformer is utilized for specific binding to a protein. However, the labile nature of glycans makes characterizing their conformational states a challenging issue. All-atom molecular dynamics (MD) simulations provide the atomic details of glycan structures in solution, but fairly extensive sampling is required for simulating the transitions between rotameric states. This difficulty limits application of conventional MD simulations to small fragments like di-and tri-saccharides. Replica-exchange molecular dynamics (REMD) simulation, with extensive sampling of structures in solution, provides a valuable way to identify a family of glycan conformers. This article reviews recent REMD simulations of glycans carried out by us or other research groups and provides new insights into the conformational equilibria of N-glycans and their alteration by chemical modification. We also emphasize the importance of statistical averaging over the multiple conformers of glycans for comparing simulation results with experimental observables. The results support the concept of "conformer selection" in protein-glycan recognition.

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“…All-atom force fields have been developed for assessing the internal structures of sugars in silico (Frank and Schloissnig, 2010; Kirschner et al, 2008) and computational modeling has been useful for generating fully glycosylated structures using the non-glycosylated template (Bohne-Lang and von der Lieth, 2005; Renouf and Hounsell, 1995). However, experimental validation of these structural models has been limited.…”

Section: Introductionmentioning

confidence: 99%

All-Atom Ensemble Modeling to Analyze Small-Angle X-Ray Scattering of Glycosylated Proteins

et al. 2013

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Summary The flexible and heterogeneous nature of carbohydrate chains often renders glycoproteins refractory to traditional structure determination methods. Small Angle X-ray scattering (SAXS) can be a useful tool for obtaining structural information of these systems. All-atom modeling of glycoproteins with flexible glycan chains was applied to interpret the solution SAXS data for a set of glycoproteins. For simpler systems (single glycan, with a well defined protein structure), all-atom modeling generates models in excellent agreement with the scattering pattern, and reveals the approximate spatial occupancy of the glycan chain in solution. For more complex systems (several glycan chains, or unknown protein substructure), the approach can still provide insightful models, though the orientations of glycans become poorly determined. Ab initio shape reconstructions appear to capture the global morphology of glycoproteins, but in most cases offer little information about glycan spatial occupancy. The all-atom modeling methodology is available as a webserver at http://modbase.compbio.ucsf.edu/allosmod-foxs.

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Bioinformatics and molecular modeling in glycobiology

Cited by 78 publications

References 243 publications

Protein-Carbohydrate Interactions Studied by NMR: From Molecular Recognition to Drug Design

Protein-Carbohydrate Interactions Studied by NMR: From Molecular Recognition to Drug Design

Conformational flexibility of N-glycans in solution studied by REMD simulations

All-Atom Ensemble Modeling to Analyze Small-Angle X-Ray Scattering of Glycosylated Proteins

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