Membrane proteins structures: A review on computational modeling tools

Almeida, José Guilherme de Andrade; Preto, António; Koukos, Panagiotis I.; Bonvin, Alexandre M. J. J.; Moreira, Irina S.

doi:10.1016/j.bbamem.2017.07.008

Cited by 85 publications

(55 citation statements)

References 325 publications

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“…Examples of this approach include the study of the lutropin receptor dimerization (Fanelli, 2007), studies aimed at characterizing the interaction interface in serotonin (5-HT) 4 (Bestel, 2005;Soulier et al, 2007) and rhodopsin complexes (Han et al, 2009), and the generation of models for the heterodimeric mGluR 2 -5-HT 2A complex (Bruno et al, 2009) and for the dopamine D 1 -D 2 receptor dimer ). -Molecular dynamics and coarse-grained simulations are one of the most versatile and widely applied computational techniques for the study of membrane proteins (Almeida et al, 2017), as they consider the tertiary structure of the studied proteins and can implement an energy landscape to estimate the molecular interactions, also accounting for the role of the lipid microenvironment. Such methods have also been used to study of GPCR dimerization and oligomerization (Fanelli et al, 2013;Jonas et al, 2015;Altwaijri et al, 2017).…”

Section: Interaction Interfacesmentioning

confidence: 99%

G protein-coupled receptor-receptor interactions give integrative dynamics to intercellular communication

Guidolin

Marcoli

Tortorella

et al. 2018

Reviews in the Neurosciences

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Abstract:The proposal of receptor-receptor interactions (RRIs) in the early 1980s broadened the view on the role of G protein-coupled receptors (GPCR) in the dynamics of the intercellular communication. RRIs, indeed, allow GPCR to operate not only as monomers but also as receptor complexes, in which the integration of the incoming signals depends on the number, spatial arrangement, and order of activation of the protomers forming the complex. The main biochemical mechanisms controlling the functional interplay of GPCR in the receptor complexes are direct allosteric interactions between protomer domains. The formation of these macromolecular assemblies has several physiologic implications in terms of the modulation of the signaling pathways and interaction with other membrane proteins. It also impacts on the emerging field of connectomics, as it contributes to set and tune the synaptic strength. Furthermore, recent evidence suggests that the transfer of GPCR and GPCR complexes between cells via the exosome pathway could enable the target cells to recognize/decode transmitters and/or modulators for which they did not express the pertinent receptors. Thus, this process may also open the possibility of a new type of redeployment of neural circuits. The fundamental aspects of GPCR complex formation and function are the focus of the present review article.

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Section: Interaction Interfacesmentioning

confidence: 99%

G protein-coupled receptor-receptor interactions give integrative dynamics to intercellular communication

Guidolin

Marcoli

Tortorella

et al. 2018

Reviews in the Neurosciences

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“…Membrane proteins represent 25% of all human proteins (Dobson, et al, 2015;Gromiha and Ou, 2014) and perform essential roles in cellular functions. Approximately 50-60% of TM proteins are drug targets for various diseases (Almeida, et al, 2017;Overington, et al, 2006) and 90% of membrane proteins present disease-associated missense mutations that may affect protein folding, stability and function (Kulandaisamy, et al, 2019). Whole genome and exome sequencing have revealed that missense mutations that are mendelian and rare disease-causing are more frequent than previously thought and collectively affect millions of patients worldwide (Chong, et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

TMSNP: a web server to predict pathogenesis of missense mutations in transmembrane region of membrane proteins

García-Recio

Gómez-Tamayo

Reina

et al. 2020

Preprint

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The massive amount of data generated from genome sequencing have given rise to several mutation predictor tools although no mutation database or predictor tool have been developed specifically for the transmembrane region of membrane proteins.We present TMSNP, a database that currently contains information from 2624 pathogenic and 195964 non-pathogenic reported mutations located on the TM region of membrane proteins. The computed conservation parameters and annotations on these mutations were used to train a machine-learning model that classifies TM mutations as pathogenic or non-pathogenic. The presented tool improves considerably the prediction power of commonly used mutation predictors and additionally represents the first mutation prediction tool specific for TM mutations.TMSNP is available at

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“…Over the years other computational techniques have advanced significantly and protein structure prediction efforts can currently be grouped into those using ab initio methods (or ab initio guided approaches) and template-based methods (fold recognition and threading, comparative modelling) [20]. Currently, protein structure prediction remains a highly active and rapidly evolving area of research [21–23]. …”

Section: Introductionmentioning

confidence: 99%

Comparison of Peptide Ion Conformers Arising from Non-Helical and Helical Peptides Using Ion Mobility Spectrometry and Gas-Phase Hydrogen/Deuterium Exchange

Karanji

Khakinejad

Kondalaji

et al. 2018

J. Am. Soc. Mass Spectrom.

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The dominant gas-phase conformer of [M+3H]3+ ions of the model peptide Acetyl-PSSSSKSSSSKSSSSKSSSSK has been examined with ion mobility spectrometry (IMS), gas-phase hydrogen deuterium exchange (HDX), and mass spectrometry (MS) techniques. The [M+3H]3+ peptide ions are observed predominantly as a relatively compact conformer type. Upon subjecting these ions to electron transfer dissociation (ETD), the level of protection for each amino acid residue in the peptide sequence is assessed. The overall per-residue deuterium uptake is observed to be relatively more efficient for the neutral residues than for the model peptide Acetyl-PAAAAKAAAAKAAAAKAAAAK. In comparison, the N-terminal and C-terminal regions of the serine peptide show greater relative protection compared with interior residues. Molecular dynamics (MD) simulations have been used to generate candidate structures for collision cross section and HDX reactivity matching. Hydrogen accessibility scoring (HAS) for select structural candidates from MD simulations has been used to suggest conformer types that could contribute to the observed HDX patterns. The results are discussed with respect to recent studies employing extensive MD simulations of gas-phase structure establishment of a peptide system.

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Membrane proteins structures: A review on computational modeling tools

Cited by 85 publications

References 325 publications

G protein-coupled receptor-receptor interactions give integrative dynamics to intercellular communication

G protein-coupled receptor-receptor interactions give integrative dynamics to intercellular communication

TMSNP: a web server to predict pathogenesis of missense mutations in transmembrane region of membrane proteins

Comparison of Peptide Ion Conformers Arising from Non-Helical and Helical Peptides Using Ion Mobility Spectrometry and Gas-Phase Hydrogen/Deuterium Exchange

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