Dynamical Methods to Study Interaction in Proteins Facilitating Molecular Understanding of Cancer

DasGupta, Bhaskar; Bekker, Gert‐Jan; Kamiya, Narutoshi

doi:10.1007/978-981-15-9411-3_149

Cited by 2 publications

(1 citation statement)

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“…Out of many established methods, elastic network models (ENMs) have been instrumental in probing the dynamics of protein-protein interactions for a number of studies, through structural perturbation methods (Zheng et al 2007; Thirumalai and Hyeon 2018), and the normal mode analysis (NMA) of oligomers and large complexes (Marcos, E., Sanchez-Martinez, M., Crehuet, R. 2014; Mishra et al 2017). In 2013 and 2014, Bhaskar, Nakamura and Kinjo observed that a counterbalance of different types of dynamics, and more speci cally the relative rigid body motions of partner molecules, dominate protein-protein binding interactions in nine different Ubiquitin-based complexes through all-atom ENMs (Dasgupta et al 2013(Dasgupta et al , 2014b(Dasgupta et al , 2020. More importantly, they found that the ligand-bound dynamics is encoded in the apo-form of Ubiquitin, exposing the power of capturing dynamics speci c to its conformational state.…”

Section: Introductionmentioning

confidence: 99%

Explicit versus implicit consideration of binding partners in protein–protein complex to elucidate intrinsic dynamics

DasGupta

Tiwari

2022

Biophys Rev

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Many proteins are involved in tightly controlled binding to other proteins by incorporating intrinsic dynamics in the binding process, which can in turn be modulated. Therefore, investigating the intrinsic dynamics of proteins is necessary to understand function in a comprehensive way. By intrinsic dynamics herein we mostly review the vibrational signature of a protein molecule popularly obtained from normal modes or essential modes. For normal modes one often considers that the molecule under investigation is a collection of springs in a solvent-free or implicit-solvent medium. However, in the context of a protein binding partner, the analysis of vibration of the target protein is often complicated due to molecular interaction within the complex. Generally, it is assumed that the isolated bound conformation of the target protein captures the implicit effect of the binding partner on the intrinsic dynamics, thereby any in uence of the partner molecule is also already integrated. Such an assumption allows large-scale studies of the conservation of protein exibility. However, in cases where a partner protein directly in uences vibration of a target via critical contacts at the protein-protein interface, the above assumption falls short of providing a detailed view. In this review, we discuss the implications of considering the dynamics of a protein in a protein-protein complex, as modelled implicitly and explicitly with methods dependent on elastic network models. We further propose how such an explicit consideration can be applied to understand critical protein-protein contacts that can be targeted in future studies. algorithm), some residue clusters using positive correlations (in black) and negative correlations (in pink) were identi ed. Corresponding clusters are shown in the context of bothstructures.

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Section: Introductionmentioning

confidence: 99%

Explicit versus implicit consideration of binding partners in protein–protein complex to elucidate intrinsic dynamics

DasGupta

Tiwari

2022

Biophys Rev

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Explicit versus implicit consideration of binding partners in protein-protein complex to elucidate intrinsic dynamics

DasGupta

Tiwari

2022

Preprint

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Many proteins are involved in tightly controlled binding to other proteins by incorporating intrinsic dynamics in the binding process, which can in turn be modulated. Therefore, investigating the intrinsic dynamics of proteins is necessary to understand function in a comprehensive way. By intrinsic dynamics herein we mostly review the vibrational signature of a protein molecule popularly obtained from normal modes or essential modes. For normal modes one often considers that the molecule under investigation is a collection of springs in a solvent-free or implicit-solvent medium. However, in the context of a protein binding partner, the analysis of vibration of the target protein is often complicated due to molecular interaction within the complex. Generally, it is assumed that the isolated bound conformation of the target protein captures the implicit effect of the binding partner on the intrinsic dynamics, thereby any influence of the partner molecule is also already integrated. Such an assumption allows large-scale studies of the conservation of protein flexibility. However, in cases where a partner protein directly influences vibration of a target via critical contacts at the protein-protein interface, the above assumption falls short of providing a detailed view. In this review, we discuss the implications of considering the dynamics of a protein in a protein-protein complex, as modelled implicitly and explicitly with methods dependent on elastic network models. We further propose how such an explicit consideration can be applied to understand critical protein-protein contacts that can be targeted in future studies.

show abstract

Dynamical Methods to Study Interaction in Proteins Facilitating Molecular Understanding of Cancer

Cited by 2 publications

References 46 publications

Explicit versus implicit consideration of binding partners in protein–protein complex to elucidate intrinsic dynamics

Explicit versus implicit consideration of binding partners in protein–protein complex to elucidate intrinsic dynamics

Explicit versus implicit consideration of binding partners in protein-protein complex to elucidate intrinsic dynamics

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