The Native State Conformational Ensemble of the SH3 Domain from α-Spectrin†

Biochemistry ◽  
1999 ◽  
Vol 38 (28) ◽  
pp. 8899-8906 ◽  
Author(s):  
Mourad Sadqi ◽  
Salvador Casares ◽  
María A. Abril ◽  
Obdulio López-Mayorga ◽  
Francisco Conejero-Lara ◽  
...  
Keyword(s):  
Sh3 Domain ◽  
Conformational Ensemble ◽  
Native State

Kinetic consequences of native state optimization of surface-exposed electrostatic interactions in the Fyn SH3 domain

2011 ◽  
Vol 80 (3) ◽  
pp. 858-870 ◽  
Author(s):  
Arash Zarrine-Afsar ◽  
Zhuqing Zhang ◽  
Katrina L. Schweiker ◽  
George I. Makhatadze ◽  
Alan R. Davidson ◽  
...  
Keyword(s):  
Electrostatic Interactions ◽  
Sh3 Domain ◽  
Native State

Self-Similarity of Protein Folding Flows

2012 ◽  
Vol 7 (4) ◽  
pp. 136-141
Author(s):  
I. Kalgin ◽  
Sergey Chekmarev
Keyword(s):  
Protein Folding ◽  
Sh3 Domain ◽  
Atomic Level ◽  
The Self ◽  
Coarse Grained ◽  
Folding Kinetics ◽  
Native State ◽  
Self Similarity ◽  
Folding Dynamics ◽  
Fractal Character

The problem of how a protein folds into its functional (native) state is one of the central problems of molecular biology, which attracts the attention of researchers from biology, physics and chemistry for many years. Of particular interest are general properties of the folding process, because the mechanisms of folding of different proteins can be essentially different. Previously, in the study of folding of fyn SH3 domain, we found that despite all the diversity and complexity of individual folding trajectories, the folding flows possess a well pronounced property of self-similarity, with a fractal character of the flow distributions. In the present paper, we study this phenomenon for another protein – beta3s, which is essentially different from the SH3 domain in its structure and folding kinetics. Also, in contrast to the fyn SH3 domain, for which a coarse-grained representation was used, we perform simulations on the atomic level of resolution. We show that the self-similarity and fractality of folding flows are observed is this case too, which suggests that these properties are characteristic of the protein folding dynamics

scholarly journals Atomic-level characterization of protein–protein association

2019 ◽  
Vol 116 (10) ◽  
pp. 4244-4249 ◽  
Author(s):  
Albert C. Pan ◽  
Daniel Jacobson ◽  
Konstantin Yatsenko ◽  
Duluxan Sritharan ◽  
Thomas M. Weinreich ◽  
...  
Keyword(s):  
Structural Information ◽  
Protein Complexes ◽  
Md Simulations ◽  
Atomic Level ◽  
Conformational Ensemble ◽  
Native State ◽  
Protein Interfaces ◽  
Study Association ◽  
Functionally Diverse

Despite the biological importance of protein–protein complexes, determining their structures and association mechanisms remains an outstanding challenge. Here, we report the results of atomic-level simulations in which we observed five protein–protein pairs repeatedly associate to, and dissociate from, their experimentally determined native complexes using a molecular dynamics (MD)–based sampling approach that does not make use of any prior structural information about the complexes. To study association mechanisms, we performed additional, conventional MD simulations, in which we observed numerous spontaneous association events. A shared feature of native association for these five structurally and functionally diverse protein systems was that if the proteins made contact far from the native interface, the native state was reached by dissociation and eventual reassociation near the native interface, rather than by extensive interfacial exploration while the proteins remained in contact. At the transition state (the conformational ensemble from which association to the native complex and dissociation are equally likely), the protein–protein interfaces were still highly hydrated, and no more than 20% of native contacts had formed.

scholarly journals A single mutation in an SH3 domain increases amyloid aggregation by accelerating nucleation, but not by destabilizing thermodynamically the native state

FEBS Letters ◽  
2009 ◽  
Vol 583 (4) ◽  
pp. 801-806 ◽  
Author(s):  
Lorena Varela ◽  
Bertrand Morel ◽  
Ana I. Azuaga ◽  
Francisco Conejero-Lara
Keyword(s):  
Sh3 Domain ◽  
Single Mutation ◽  
Amyloid Aggregation ◽  
Native State

scholarly journals Molecular dynamics ensemble refinement of the heterogeneous native state of NCBD using chemical shifts and NOEs

2018 ◽  
Author(s):  
Elena Papaleo ◽  
Carlo Camilloni ◽  
Kaare Teilum ◽  
Michele Vendruscolo ◽  
Kresten Lindorff-Larsen
Keyword(s):  
Force Field ◽  
Chemical Shifts ◽  
Molten Globule ◽  
Conformational Dynamics ◽  
Nmr Relaxation ◽  
Structural Heterogeneity ◽  
Order Parameters ◽  
Protein Domain ◽  
Conformational Ensemble ◽  
Native State

ABSTRACTMany proteins display complex dynamical properties that are often intimately linked to their biological functions. As the native state of a protein is best described as an ensemble of confor-mations, it is important to be able to generate models of native state ensembles with high accuracy. Due to limitations in sampling efficiency and force field accuracy it is, however, challenging to obtain accurate ensembles of protein conformations by the use of molecular simulations alone. Here we show that dynamic ensemble refinement, which combines an accurate atomistic force field with commonly available nuclear magnetic resonance (NMR) chemical shifts and NOEs, can provide a detailed and accurate description of the conformational ensemble of the native state of a highly dynamic protein. As both NOEs and chemical shifts are averaged on timescales up to milliseconds, the resulting ensembles reflect the structural heterogeneity that goes beyond that probed e.g. by NMR relaxation order parameters. We selected the small protein domain NCBD as object of our study since this protein, which has been characterized experimentally in substantial detail, displays a rich and complex dynamical behaviour. In particular, the protein has been described as having a molten-globule like structure, but with a relatively rigid core. Our approach allowed us to describe the conformational dynamics of NCBD in solution, and to probe the structural heterogeneity resulting from both short- and long-time-scale dynamics by the calculation of order parameters on different time scales. These results illustrate the usefulness of our approach since they show that NCBD is rather rigid on the nanosecond timescale, but interconverts within a broader ensemble on longer timescales, thus enabling the derivation of a coherent set of conclusions from various NMR experiments on this protein, which could otherwise appear in contradiction with each other.

scholarly journals Molecular dynamics ensemble refinement of the heterogeneous native state of NCBD using chemical shifts and NOEs

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5125 ◽  
Author(s):  
Elena Papaleo ◽  
Carlo Camilloni ◽  
Kaare Teilum ◽  
Michele Vendruscolo ◽  
Kresten Lindorff-Larsen
Keyword(s):  
Force Field ◽  
Chemical Shifts ◽  
Molten Globule ◽  
Conformational Dynamics ◽  
Nmr Relaxation ◽  
Structural Heterogeneity ◽  
Order Parameters ◽  
Protein Domain ◽  
Conformational Ensemble ◽  
Native State

Many proteins display complex dynamical properties that are often intimately linked to their biological functions. As the native state of a protein is best described as an ensemble of conformations, it is important to be able to generate models of native state ensembles with high accuracy. Due to limitations in sampling efficiency and force field accuracy it is, however, challenging to obtain accurate ensembles of protein conformations by the use of molecular simulations alone. Here we show that dynamic ensemble refinement, which combines an accurate atomistic force field with commonly available nuclear magnetic resonance (NMR) chemical shifts and NOEs, can provide a detailed and accurate description of the conformational ensemble of the native state of a highly dynamic protein. As both NOEs and chemical shifts are averaged on timescales up to milliseconds, the resulting ensembles reflect the structural heterogeneity that goes beyond that probed, e.g., by NMR relaxation order parameters. We selected the small protein domain NCBD as object of our study since this protein, which has been characterized experimentally in substantial detail, displays a rich and complex dynamical behaviour. In particular, the protein has been described as having a molten-globule like structure, but with a relatively rigid core. Our approach allowed us to describe the conformational dynamics of NCBD in solution, and to probe the structural heterogeneity resulting from both short- and long-timescale dynamics by the calculation of order parameters on different time scales. These results illustrate the usefulness of our approach since they show that NCBD is rather rigid on the nanosecond timescale, but interconverts within a broader ensemble on longer timescales, thus enabling the derivation of a coherent set of conclusions from various NMR experiments on this protein, which could otherwise appear in contradiction with each other.

scholarly journals Atomic-level characterization of protein-protein association

2018 ◽  
Author(s):  
Albert C. Pan ◽  
Daniel Jacobson ◽  
Konstantin Yatsenko ◽  
Duluxan Sritharan ◽  
Thomas M. Weinreich ◽  
...  
Keyword(s):  
Structural Information ◽  
Protein Complexes ◽  
Md Simulations ◽  
Atomic Level ◽  
Conformational Ensemble ◽  
Native State ◽  
Protein Interfaces ◽  
Study Association ◽  
Functionally Diverse

Despite the biological importance of protein-protein complexes, determining their structures and association mechanisms remains an outstanding challenge. Here, we report the results of atomic-level simulations in which we observed five protein-protein pairs repeatedly associate to, and dissociate from, their experimentally determined native complexes using a new molecular dynamics (MD)-based sampling approach that does not make use of any prior structural information about the complexes. To study association mechanisms, we performed additional, conventional MD simulations, in which we observed numerous spontaneous association events. A shared feature of native association for these five structurally and functionally diverse protein systems was that if the proteins made contact far from the native interface, the native state was reached by dissociation and eventual re-association near the native interface, rather than by extensive interfacial exploration while the proteins remained in contact. At the transition state (the conformational ensemble from which association to the native complex and dissociation are equally likely), the protein-protein interfaces were still highly hydrated, and no more than 20% of native contacts had formed.

scholarly journals NMR characterizations of an amyloidogenic conformational ensemble of the PI3K SH3 domain

2006 ◽  
Vol 15 (11) ◽  
pp. 2552-2557 ◽  
Author(s):  
Hee-Chul Ahn ◽  
Yen T.H. Le ◽  
Partha S. Nagchowdhuri ◽  
Eugene F. DeRose ◽  
Cindy Putnam-Evans ◽  
...  
Keyword(s):  
Sh3 Domain ◽  
Conformational Ensemble
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