Vibrational Energy in Proteins Correlates with Topology

Maggi, Luca; Carloni, Paolo; Rossetti, Giulia

doi:10.1021/acs.jpclett.8b02380

Cited by 10 publications

(13 citation statements)

References 23 publications

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“…According to PCCA+, the two recognized clusters represents regions in which the E vib exchange processes among residues within the cluster is faster than the E vib exchange between the clusters themselves. This finding agrees with previously reported computational results showing that residues belonging to the regions identified by the clusters feature shorter characteristic time for E vib exchange 19 .…”

Section: Resultssupporting

confidence: 93%

“…and E vib but just their ratio p i (t)). L is the transition frequency matrix, whose elements L ij are the frequencies associated with transition times τ ij , which are the characteristic time to exchange E vib between residue i and j, as calculated in reference 19 . Each element of L is defined as:…”

Section: Resultsmentioning

confidence: 99%

“…1), except those belonging to the third intracellular loop. Due to its high mobility, indeed, the approximations needed for calculating τ ij no longer holds 19 and all the possible values becomes unreliable. The loop is included in our MD simulations (see Methods).…”

Section: Resultsmentioning

confidence: 99%

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Modeling the allosteric modulation on a G-Protein Coupled Receptor: the case of M2 muscarinic Acetylcholine Receptor in complex with LY211960

Maggi

Carloni

Rossetti

2020

Sci Rep

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Allosteric modulation is involved in a plethora of diverse protein functions, which are fundamental for cells' life. this phenomenon can be thought as communication between two topographically distinct site of a protein structure. How this communication occurs is still matter of debate. Many different descriptions have been presented so far. Here we consider a specific case where any significant conformational change is involved upon allosteric modulator binding and the phenomenon is depicted as a vibrational energy diffusion process between distant protein regions. We applied this model, by employing computational tools, to the human muscarinic receptor M2, a transmembrane protein G-protein coupled receptor known to undergo allosteric modulation whose recently X-ray structure has been recently resolved both with and without the presence of a particular allosteric modulator. our calculations, performed on these two receptor structures, suggest that for this case the allosteric modulator modifies the energy current between functionally relevant regions of the protein; this allows to identify the main residues responsible for this modulation. these results contribute to shed light on the molecular basis of allosteric modulation and may help design new allosteric ligands. Allosteric modulation of proteins, discovered more than fifty years ago 1 , plays an important role for many processes, from signal transduction 2 to transcriptional regulations 3. This phenomenon regards any molecular event in which the binding of a ligand in a specific region of a protein (allosteric binding site) affects the stability of distant "primary" binding site (often referred as orthosteric binding site) 4,5. The term allosteric is coined for the first time by Monod, Wyman and Changeux within the WMC model 6. According to it, proteins can assume two different conformations, each of them exhibiting different binding affinity for the orthosteric ligand. The allosteric ligands can affect the thermodynamic stability of this conformations modifying, consequently, the orthosteric binding affinity. This model implies a protein conformational change mediating the interaction between the two distant sites. However, it has been shown that the allosteric binding site can affect the orthosteric binding also without involving any conformational rearrangement 7 , modifying, for instance, proteins vibrations around their thermodynamic stable conformations 7. These different types of allosteric modulation share a common and peculiar feature, namely the presence of a long-range communication between two different sites of a protein 8. Allosteric modulators can be distinguished on the basis of their contribution to the free energy of binding. In the case that such contribution is manly enthalpic, (Type I), it usually leads to a conformational change 9. In contrast, when entropic contribution is prevalent (Type II), molecular vibrations are

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Section: Resultssupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

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Modeling the allosteric modulation on a G-Protein Coupled Receptor: the case of M2 muscarinic Acetylcholine Receptor in complex with LY211960

Maggi

Carloni

Rossetti

2020

Sci Rep

Self Cite

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“…The study of vibrational energy relaxation in proteins, ,,,− part of a long-standing goal of describing relaxation dynamics in complex molecular environments, − has led to a search for relatively simple models that capture its main features. This has included studies addressing the role of structure and bonding, dynamics, ,,− and quantum mechanical effects. − Coarse-grain modeling using a classical master equation offers a promising approach to model energy transport in proteins and protein complexes, ,, identifying regions along which transport is facile and reproducing energy dynamics quite well when compared with results of all-atom simulations. The master equation simulations support a diffusion-like picture for transport.…”

Section: Introductionmentioning

confidence: 99%

Energy Transfer across Nonpolar and Polar Contacts in Proteins: Role of Contact Fluctuations

et al. 2020

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Molecular dynamics simulations of the villin headpiece subdomain HP36 have been carried out to examine relations between rates of vibrational energy transfer across noncovalently bonded contacts and equilibrium structural fluctuations, with focus on van der Waals contacts. Rates of energy transfer across van der Waals contacts vary inversely with the variance of the contact length, with the same constant of proportionality for all nonpolar contacts of HP36. A similar relation is observed for hydrogen bonds, but the proportionality depends on contact pairs, with hydrogen bonds stabilizing the α-helices all exhibiting the same constant of proportionality, one that is distinct from those computed for other polar contacts. Rates of energy transfer across van der Waals contacts are found to be up to 2 orders of magnitude smaller than rates of energy transfer across polar contacts.

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“…On length scales from about 2 Å to several nm, proteins exhibit properties of fractal objects, which provide a statistical description of energy transport and the emergence of networks of energy transport channels that span these molecules. − The statistical similarity between the distribution of mass on the level of amino acids and at larger length scales of groups of amino acids has been associated with the subdiffusive energy dynamics observed in computational studies, vibrational dynamics of proteins, − and the anisotropy of energy transfer observed in time-resolved vibrational spectroscopy. , Statistical properties of mass distribution indicate that energy transport is anisotropic and networks for long-range energy transport are ubiquitous in globular proteins. Networks of energy transport in proteins and between protein molecules, including long-range nonbonded networks in allosteric proteins that also include water molecules, , have been identified by computational studies ,− and probed by experiment. ,,,− …”

Section: Introductionmentioning

confidence: 99%

Energy Transport across Interfaces in Biomolecular Systems

2019

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Energy transport during chemical reactions or following photoexcitation in systems of biological molecules is mediated by numerous interfaces that separate chemical groups and molecules. Describing and predicting energy transport has been complicated by the inhomogeneous environment through which it occurs, and general rules are still lacking. We discuss recent work on identification of networks for vibrational energy transport in biomolecules and their environment, with focus on the nature of energy transfer across interfaces. Energy transport is influenced both by structure of the biomolecular system as well as by equilibrium fluctuations of nonbonded contacts between chemical groups, biomolecules, and water along the network. We also discuss recent theoretical and computational work on the related topic of thermal transport through molecular interfaces, with focus on systems important in biology as well as relevant experimental studies.

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Vibrational Energy in Proteins Correlates with Topology

Cited by 10 publications

References 23 publications

Modeling the allosteric modulation on a G-Protein Coupled Receptor: the case of M2 muscarinic Acetylcholine Receptor in complex with LY211960

Modeling the allosteric modulation on a G-Protein Coupled Receptor: the case of M2 muscarinic Acetylcholine Receptor in complex with LY211960

Energy Transfer across Nonpolar and Polar Contacts in Proteins: Role of Contact Fluctuations

Energy Transport across Interfaces in Biomolecular Systems

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