Computational molecular biology approaches to ligand‐target interactions

Lupieri, Paola; Nguyen, Chuong; Bafghi, Zhaleh Ghaemi; Giorgetti, Alejandro; Carloni, Paolo

doi:10.2976/1.3092784

Cited by 11 publications

(8 citation statements)

References 103 publications

(105 reference statements)

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“…Our group and collaborators have been involved, during the last decade, in the application of a combination of computational and experimental techniques aimed at the unravelling of the molecular mechanisms underlying the different steps of several signalling cascades, i.e. vision, olfaction and bitter taste, all of them including GPCRs as the initial part of the signalling firing event [22][23][24][25][26][27][28]. In fact, we have to consider that the main challenges for the near future will include the development and application of methods that permit the full description at the molecular/structural level of GPCR-ligand complexes, as they constitute one of the principal drug targets in the human organism.…”

Section: Resultsmentioning

confidence: 99%

OlfactionDB: A Database of Olfactory Receptors and Their Ligands

Modena¹,

Trentini²,

Corsini³

et al. 2012

ALS

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Odorants are volatile molecules that efficiently carry chemical information, providing one of the main ways for communicating with the environment in all kingdoms of life. In the other hand, mammalian genomes codify for hundreds of olfactory receptors (ORs), e.g. about 400 in human and more than 1000 in mouse, underlying the crucial role of the sense of smell during evolution. Therefore, the olfactory system is capable to discriminate between ~10,000 different odors. The possibility of collecting and compiling information about odorants and their receptors is thus fundamental for a functional characterization of the signaling firing event. OlfactionDB, a manually curated database providing comprehensive information for nearly 400 odorant-receptor interactions at the current state, has been developed for managing information about odorants and their receptors. OlfactionDB is a free publicly database available online from: http://molsim.sci.univr.it/OlfactionDB.

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Section: Resultsmentioning

confidence: 99%

OlfactionDB: A Database of Olfactory Receptors and Their Ligands

Modena¹,

Trentini²,

Corsini³

et al. 2012

ALS

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“…So far, structures for olfactory receptors have not been resolved crystallographically [36, 37], though structures of other G-protein coupled receptors are available [38–41]. Based on the available structures, models of olfactory receptors have been built, mainly by Goddard and coworkers [42–45], but also by others [46, 47]. In fact, models for a variety of odorants and receptors of different organisms were constructed; recently even automated modeling of mammalian olfactory receptors and docking of odorants has been reported [48].…”

Section: Discussionmentioning

confidence: 99%

Vibrationally assisted electron transfer mechanism of olfaction: myth or reality?

Solov’yov

Chang

Schulten

2012

Phys. Chem. Chem. Phys.

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Smell is a vital sense for animals. The mainstream explanation of smell is based on recognition of the odorant molecules through characteristics of their surface, e.g., shape, but certain experiments suggest that such recognition is complemented by recognition of vibrational modes. According to this suggestion an olfactory receptor is activated by electron transfer assisted through odorant vibrational excitation. The hundreds to thousands of different olfactory receptors in an animal recognize odorants over a discriminant landscape with surface properties and vibrational frequencies as the two major dimensions. In the present paper we introduce the vibrationally assisted mechanism of olfaction and demonstrate for several odorants that, indeed, a strong enhancement of an electron tunneling rate due to odorant vibrations can arise. We discuss in this regard the influence of odorant deuteration and explain, thereby, recent experiments performed on Drosophila melanogaster. Our demonstration is based on known physical properties of biological electron transfer and on ab initio calculations on odorants carried out for the purpose of the present study. We identify a range of physical characteristics which olfactory receptors and odorants must obey for the vibrationally assisted electron transfer mechanism to function. We argue that the stated characteristics are feasible for realistic olfactory receptors, noting, though, that the receptor structure presently is still unknown, but can be studied through homology modeling.

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“…But this is not the case here, it is not easy to know the structure of integral proteins [36,37], including olfactory receptor. It is the topic of ongoing researches, using various methods like Molecular Dynamic (MD) simulations, mutagenesis studies, heterologus expression studies, and homology modeling [38][39][40][41][42][43][44][45][46].…”

Section: Introductionmentioning

confidence: 91%

Olfactory receptors are sensitive to molecular volume of odorants

Saberi

Seyed-allaei

2015

Preprint

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To study olfaction, first we should know which physical or chemical properties of odorant molecules determine the response of olfactory receptor neurons, and then we should study the effect of those properties on the combinatorial encoding in olfactory system.In this work we show that the response of an olfactory receptor neuron in Drosophila depends on molecular volume of an odorant; The molecular volume determines the upper limits of the neural response, while the actual neural response may depend on other properties of the molecules. Each olfactory receptor prefers a particular volume, with some degree of flexibility. These two parameters predict the volume and flexibility of the binding-pocket of the olfactory receptors, which are the targets of structural biology studies.At the end we argue that the molecular volume can affects the quality of perceived smell of an odorant via the combinatorial encoding, molecular volume may mask other underlying relations between properties of molecules and neural responses and we suggest a way to improve the selection of odorants in further experimental studies.

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Computational molecular biology approaches to ligand‐target interactions

Cited by 11 publications

References 103 publications

OlfactionDB: A Database of Olfactory Receptors and Their Ligands

OlfactionDB: A Database of Olfactory Receptors and Their Ligands

Vibrationally assisted electron transfer mechanism of olfaction: myth or reality?

Olfactory receptors are sensitive to molecular volume of odorants

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