scholarly journals Conformational ensemble of human α-synuclein physiological form predicted by molecular simulations

2016 ◽  
Vol 18 (8) ◽  
pp. 5702-5706 ◽  
Author(s):  
G. Rossetti ◽  
F. Musiani ◽  
E. Abad ◽  
D. Dibenedetto ◽  
H. Mouhib ◽  
...  
Keyword(s):  
Protein Dynamics ◽  
Molecular Simulations ◽  
Intramolecular Interactions ◽  
Conformational Ensemble ◽  
Enhanced Sampling ◽  
Post Translational Modification ◽  
Α Helix

Enhanced sampling simulations of N-terminally acetylated human α-synuclein suggest that the post-translational modification leads to the formation of a transient amphipathic α-helix altering protein dynamics at the N-terminal and intramolecular interactions.

scholarly journals Extended Phase-Space Methods for Enhanced Sampling in Molecular Simulations: A Review

2015 ◽  
Vol 3 ◽  
Author(s):  
Hiroshi Fujisaki ◽  
Kei Moritsugu ◽  
Yasuhiro Matsunaga ◽  
Tetsuya Morishita ◽  
Luca Maragliano
Keyword(s):  
Phase Space ◽  
Molecular Simulations ◽  
Extended Phase Space ◽  
Enhanced Sampling ◽  
Extended Phase ◽  
Phase Space Methods

scholarly journals Post-translational modification of barley LTP1b: The lipid adduct lies in the hydrophobic cavity and alters the protein dynamics

FEBS Letters ◽  
2007 ◽  
Vol 581 (24) ◽  
pp. 4557-4561 ◽  
Author(s):  
Ramani Wijesinha-Bettoni ◽  
Chunli Gao ◽  
John A. Jenkins ◽  
Alan R. Mackie ◽  
Peter J. Wilde ◽  
...  
Keyword(s):  
Protein Dynamics ◽  
Post Translational Modification ◽  
Hydrophobic Cavity

scholarly journals How to Determine Accurate Conformational Ensembles by Metadynamics Metainference: A Chignolin Study Case

2021 ◽  
Vol 8 ◽  
Author(s):  
Cristina Paissoni ◽  
Carlo Camilloni
Keyword(s):  
Experimental Data ◽  
Molecular Dynamics ◽  
Experimental Information ◽  
Conformational Ensemble ◽  
Enhanced Sampling ◽  
Conformational Ensembles ◽  
Statistical Precision ◽  
Minimum Number ◽  
Study Case ◽  
Dynamics Simulations

The reliability and usefulness of molecular dynamics simulations of equilibrium processes rests on their statistical precision and their capability to generate conformational ensembles in agreement with available experimental knowledge. Metadynamics Metainference (M&M), coupling molecular dynamics with the enhanced sampling ability of Metadynamics and with the ability to integrate experimental information of Metainference, can in principle achieve both goals. Here we show that three different Metadynamics setups provide converged estimate of the populations of the three-states populated by a model peptide. Errors are estimated correctly by block averaging, but higher precision is obtained by performing independent replicates. One effect of Metadynamics is that of dramatically decreasing the number of effective frames resulting from the simulations and this is relevant for M&M where the number of replicas should be large enough to capture the conformational heterogeneity behind the experimental data. Our simulations allow also us to propose that monitoring the relative error associated with conformational averaging can help to determine the minimum number of replicas to be simulated in the context of M&M simulations. Altogether our data provides useful indication on how to generate sound conformational ensemble in agreement with experimental data.

scholarly journals Molecular Dynamics Simulations of Phosphorylated Intrinsically Disordered Proteins: A Force Field Comparison

2021 ◽  
Vol 22 (18) ◽  
pp. 10174
Author(s):  
Ellen Rieloff ◽  
Marie Skepö
Keyword(s):  
Force Field ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Conformational Ensemble ◽  
Salt Bridges ◽  
Post Translational Modification ◽  
Intrinsically Disordered ◽  
The Difference ◽  
Disordered Peptides ◽  
Dynamics Simulations

Phosphorylation is a common post-translational modification among intrinsically disordered proteins and regions, which helps regulate function by changing the protein conformations, dynamics, and interactions with binding partners. To fully comprehend the effects of phosphorylation, computer simulations are a helpful tool, although they are dependent on the accuracy of the force field used. Here, we compared the conformational ensembles produced by Amber ff99SB-ILDN+TIP4P-D and CHARMM36m, for four phosphorylated disordered peptides ranging in length from 14–43 residues. CHARMM36m consistently produced more compact conformations with a higher content of bends, mainly due to more stable salt bridges. Based on comparisons with experimental size estimates for the shortest and longest peptide, CHARMM36m appeared to overestimate the compactness. The difference between the force fields was largest for the peptide showing the greatest separation between positively charged and phosphorylated residues, in line with the importance of charge distribution. For this peptide, the conformational ensemble did not change significantly upon increasing the ionic strength from 0 mM to 150 mM, despite a reduction of the salt-bridging probability in the CHARMM36m simulations, implying that salt concentration has negligible effects in this study.

scholarly journals Biomolecular conformational changes and ligand binding: from kinetics to thermodynamics

2017 ◽  
Vol 8 (9) ◽  
pp. 6466-6473 ◽  
Author(s):  
Yong Wang ◽  
João Miguel Martins ◽  
Kresten Lindorff-Larsen
Keyword(s):  
Ligand Binding ◽  
Conformational Changes ◽  
Molecular Simulations ◽  
Kinetic Properties ◽  
Enhanced Sampling ◽  
Biomolecular Systems

Biomolecular systems such as protein–ligand complexes are governed by thermodynamic and kinetic properties that may be estimated at the same time through enhanced-sampling molecular simulations.

scholarly journals Assignment of the resting state of the secondary active transporter BetP by integrating spectroscopic measurements and molecular simulations

2018 ◽  
Author(s):  
Vanessa Leone ◽  
Izabela Waclawska ◽  
Caroline Koshy ◽  
Katharina Kossman ◽  
Monika Sharma ◽  
...  
Keyword(s):  
Double Resonance ◽  
Molecular Simulations ◽  
Enhanced Sampling ◽  
Experimental Conditions ◽  
Physiological Conditions ◽  
Data Comparison ◽  
Osmotic Stress Response ◽  
Biochemical Studies ◽  
Transport Cycle ◽  
Crystallographic Structures

The glycine betaine symporter BetP regulates the osmotic stress response of Corynebacterium glutamicum, a soil bacterium used extensively in biotechnology. Although BetP is a homotrimer, biochemical studies have shown that each protomer is able to transport its substrate independently. Crystallographic structures of BetP have been determined in several conformations, seemingly capturing outward-open, inward-open and occluded states, both loaded with the substrate and in the apo form. However, it has been challenging to establish a correspondence between each of these structures and specific states in the mechanism of the transporter under more physiological conditions. To this end, we examined the dynamics of spin-labelled BetP using pulsed electron-electron double resonance (PELDOR) under different stimuli. We then carried out molecular simulations of structures of the BetP monomer to interpret the PELDOR data, using the enhanced-sampling methodology EBMetaD [Marinelli & Faraldo-Gomez, 2015, Biophys J 108(12):2779-2782], whereby the dynamics of the protein are minimally biased so as to reproduce the experimental data. Comparison of the magnitude of the biasing work required for different input structures permitted us to assign them to specific states of the transport cycle under each of the experimental conditions. In particular, this analysis showed that BetP adopts inward-facing conformations in the presence of excess sodium, and a mixture of states when betaine is added. These studies better delineate the major conformations adopted by BetP in its transport cycle, and therefore provide important insights into its mechanism. More broadly, we illustrate how integrative simulations can aid interpretation of ambiguous structural and spectroscopic data on membrane proteins.

scholarly journals A different perspective for nonphotochemical quenching in plant antenna complexes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Edoardo Cignoni ◽  
Margherita Lapillo ◽  
Lorenzo Cupellini ◽  
Silvia Acosta-Gutiérrez ◽  
Francesco Luigi Gervasio ◽  
...  
Keyword(s):  
Light Harvesting ◽  
Nonphotochemical Quenching ◽  
Dual Function ◽  
Conformational Ensemble ◽  
Coulomb Interactions ◽  
Enhanced Sampling ◽  
Excitation Energies ◽  
Light Harvesting Complexes ◽  
Quenching Mechanisms ◽  
A Minor

AbstractLight-harvesting complexes of plants exert a dual function of light-harvesting (LH) and photoprotection through processes collectively called nonphotochemical quenching (NPQ). While LH processes are relatively well characterized, those involved in NPQ are less understood. Here, we characterize the quenching mechanisms of CP29, a minor LHC of plants, through the integration of two complementary enhanced-sampling techniques, dimensionality reduction schemes, electronic calculations and the analysis of cryo-EM data in the light of the predicted conformational ensemble. Our study reveals that the switch between LH and quenching state is more complex than previously thought. Several conformations of the lumenal side of the protein occur and differently affect the pigments’ relative geometries and interactions. Moreover, we show that a quenching mechanism localized on a single chlorophyll-carotenoid pair is not sufficient but many chlorophylls are simultaneously involved. In such a diffuse mechanism, short-range interactions between each carotenoid and different chlorophylls combined with a protein-mediated tuning of the carotenoid excitation energies have to be considered in addition to the commonly suggested Coulomb interactions.

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