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Structural Transition States Explored With Minimalist Coarse Grained Models: Applications to Calmodulin. / Delfino, Francesco; Porozov, Yuri; Stepanov, Eugene ; Tamazian, Gaik ; Tozzini, Valentina.

в: Frontiers in Molecular Biosciences, Том 6, № 104, 104, 10.2019.

Результаты исследований: Научные публикации в периодических изданияхстатьяРецензирование

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Delfino, Francesco ; Porozov, Yuri ; Stepanov, Eugene ; Tamazian, Gaik ; Tozzini, Valentina. / Structural Transition States Explored With Minimalist Coarse Grained Models: Applications to Calmodulin. в: Frontiers in Molecular Biosciences. 2019 ; Том 6, № 104.

BibTeX

@article{a1f16ce1e758472f8ca891e74f2f5cc6,
title = "Structural Transition States Explored With Minimalist Coarse Grained Models: Applications to Calmodulin",
abstract = "Transitions between different conformational states are ubiquitous in proteins, being involved in signaling, catalysis, and other fundamental activities in cells. However, modeling those processes is extremely difficult, due to the need of efficiently exploring a vast conformational space in order to seek for the actual transition path for systems whose complexity is already high in the stable states. Here we report a strategy that simplifies this task attacking the complexity on several sides. We first apply a minimalist coarse-grained model to Calmodulin, based on an empirical force field with a partial structural bias, to explore the transition paths between the apo-closed state and the Ca-bound open state of the protein. We then select representative structures along the trajectory based on a structural clustering algorithm and build a cleaned-up trajectory with them. We finally compare this trajectory with that produced by the online tool MinActionPath, by minimizing the action integral using a harmonic network model, and with that obtained by the PROMPT morphing method, based on an optimal mass transportation-type approach including physical constraints. The comparison is performed both on the structural and energetic level, using the coarse-grained and the atomistic force fields upon reconstruction. Our analysis indicates that this method returns trajectories capable of exploring intermediate states with physical meaning, retaining a very low computational cost, which can allow systematic and extensive exploration of the multi-stable proteins transition pathways.",
keywords = "биоинформатика, classical molecular dynamics, coarse grained models, minimal action path, PROMPT, proteins conformational transitions, transition path sampling",
author = "Francesco Delfino and Yuri Porozov and Eugene Stepanov and Gaik Tamazian and Valentina Tozzini",
year = "2019",
month = oct,
doi = "10.3389/fmolb.2019.00104",
language = "English",
volume = "6",
journal = "Frontiers in Molecular Biosciences",
issn = "2296-889X",
publisher = "Frontiers Media S.A.",
number = "104",

}

RIS

TY - JOUR

T1 - Structural Transition States Explored With Minimalist Coarse Grained Models: Applications to Calmodulin

AU - Delfino, Francesco

AU - Porozov, Yuri

AU - Stepanov, Eugene

AU - Tamazian, Gaik

AU - Tozzini, Valentina

PY - 2019/10

Y1 - 2019/10

N2 - Transitions between different conformational states are ubiquitous in proteins, being involved in signaling, catalysis, and other fundamental activities in cells. However, modeling those processes is extremely difficult, due to the need of efficiently exploring a vast conformational space in order to seek for the actual transition path for systems whose complexity is already high in the stable states. Here we report a strategy that simplifies this task attacking the complexity on several sides. We first apply a minimalist coarse-grained model to Calmodulin, based on an empirical force field with a partial structural bias, to explore the transition paths between the apo-closed state and the Ca-bound open state of the protein. We then select representative structures along the trajectory based on a structural clustering algorithm and build a cleaned-up trajectory with them. We finally compare this trajectory with that produced by the online tool MinActionPath, by minimizing the action integral using a harmonic network model, and with that obtained by the PROMPT morphing method, based on an optimal mass transportation-type approach including physical constraints. The comparison is performed both on the structural and energetic level, using the coarse-grained and the atomistic force fields upon reconstruction. Our analysis indicates that this method returns trajectories capable of exploring intermediate states with physical meaning, retaining a very low computational cost, which can allow systematic and extensive exploration of the multi-stable proteins transition pathways.

AB - Transitions between different conformational states are ubiquitous in proteins, being involved in signaling, catalysis, and other fundamental activities in cells. However, modeling those processes is extremely difficult, due to the need of efficiently exploring a vast conformational space in order to seek for the actual transition path for systems whose complexity is already high in the stable states. Here we report a strategy that simplifies this task attacking the complexity on several sides. We first apply a minimalist coarse-grained model to Calmodulin, based on an empirical force field with a partial structural bias, to explore the transition paths between the apo-closed state and the Ca-bound open state of the protein. We then select representative structures along the trajectory based on a structural clustering algorithm and build a cleaned-up trajectory with them. We finally compare this trajectory with that produced by the online tool MinActionPath, by minimizing the action integral using a harmonic network model, and with that obtained by the PROMPT morphing method, based on an optimal mass transportation-type approach including physical constraints. The comparison is performed both on the structural and energetic level, using the coarse-grained and the atomistic force fields upon reconstruction. Our analysis indicates that this method returns trajectories capable of exploring intermediate states with physical meaning, retaining a very low computational cost, which can allow systematic and extensive exploration of the multi-stable proteins transition pathways.

KW - биоинформатика

KW - classical molecular dynamics

KW - coarse grained models

KW - minimal action path

KW - PROMPT

KW - proteins conformational transitions

KW - transition path sampling

UR - http://www.scopus.com/inward/record.url?scp=85074326974&partnerID=8YFLogxK

U2 - 10.3389/fmolb.2019.00104

DO - 10.3389/fmolb.2019.00104

M3 - Article

VL - 6

JO - Frontiers in Molecular Biosciences

JF - Frontiers in Molecular Biosciences

SN - 2296-889X

IS - 104

M1 - 104

ER -

ID: 49559086