Protein flexibility: Multiple molecular dynamics simulations of insulin chain B

Legge, Fiona S.; Budi, Akin; Treutlein, Herbert; Yarovsky, Irene

doi:10.1016/j.bpc.2005.08.002

Cited by 56 publications

(88 citation statements)

References 63 publications

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“…Secondly, if these variations in the flexibilities are intrinsic, then, for studying flexibility changes which are caused by any local structural alterations, such as protein mutations, modifications, and ligand binding, these variations must be considered in designing of the method. For example, regarding these type of studies which have been done using MD simulation, there is a method called as Multiple Molecular Dynamics (MMD) Simulation (14)(15)(16). In this method of MD simulation for one beginning snapshot, multiple repeats will be run with just different initial velocities and an average of the results will be considered or, at least, all the repeats will be notified.…”

Section: Different Initial Conditions Between Three MD Trajectories Omentioning

confidence: 99%

“…The objective of their research was to compare NMR driven flexibility with MD simulation ones (12). Also, there were a number of studies which have used a method called as the Multiple Molecular Dynamics Simulation (MMDS) (13)(14)(15)(16)(17). However, MD simulations will be repeated with exactly the same initial snapshots in this method, while the initial snapshots of the repeating MD simulations have some differences with each other in our method.…”

Section: Introductionmentioning

confidence: 99%

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Variability of the Cyclin-Dependent Kinase 2 Flexibility Without Significant Change in the Initial Conformation of the Protein or Its Environment; a Computational Study

2016

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Protein flexibility probably is a phenomenon that can make the existence of the many protein conformations possible in contrast to a limited number. Many conformations in a protein are needed for doing many functions. For instance, based on searching IntAct PPI database with the UniprotKB accession number of hCDK2: P24941, hCDK2 has at least 200 different interactions with other proteins in addition to interactions by itself (1). As a structural characteristic, protein flexibility plays many functional roles with respect to different aspects of the proteins as well. Examples in this regard are enzyme catalysis and ligand-receptor interactions, substrate and ligand orientation, the turnover rate of the substrates, and reduction of the free energy barrier in the active sites (2).In structural bioinformatics tools, there are many instances regarding protein flexibility applications and usefulness; as an example, improvement of the small ligand-receptor docking (3,4 Background: Protein flexibility, which has been referred as a dynamic behavior has various roles in proteins' functions. Furthermore, for some developed tools in bioinformatics, such as protein-protein docking software, considering the protein flexibility, causes a higher degree of accuracy. Through undertaking the present work, we have accomplished the quantification plus analysis of the variations in the human Cyclin Dependent Kinase 2 (hCDK2) protein flexibility without affecting a significant change in its initial environment or the protein per se. Objectives:The main goal of the present research was to calculate variations in the flexibility for each residue of the hCDK2, analysis of their flexibility variations through clustering, and to investigate the functional aspects of the residues with high flexibility variations. Materials and Methods: Using Gromacs package (version 4.5.4), three independent molecular dynamics (MD) simulations of the hCDK2 protein (PDB ID: 1HCL) was accomplished with no significant changes in their initial environments, structures, or conformations, followed by Root Mean Square Fluctuations (RMSF) calculation of these MD trajectories. The amount of variations in these three curves of RMSF was calculated using two formulas.Results: More than 50% of the variation in the flexibility (the distance between the maximum and the minimum amount of the RMSF) was found at the region of Val-154. As well, there are other major flexibility fluctuations in other residues. These residues were mostly positioned in the vicinity of the functional residues. The subsequent works were done, as followed by clustering all hCDK2 residues into four groups considering the amount of their variability with respect to flexibility and their position in the RMSF curves. Conclusions:This work has introduced a new class of flexibility aspect of the proteins' residues. It could also help designing and engineering proteins, with introducing a new dynamic aspect of hCDK2, and accordingly, for the other similar globular proteins. In addition, it could provide a...

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Section: Different Initial Conditions Between Three MD Trajectories Omentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Variability of the Cyclin-Dependent Kinase 2 Flexibility Without Significant Change in the Initial Conformation of the Protein or Its Environment; a Computational Study

2016

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“…Yet charges in pH can also affect the structure. Then it enables a broad sampling of the conformational states of a protein under controlled conditions and therefore delivers additional understanding of the protein dynamics [12]. Simulation of molecular dynamics (MD) could provide continuous dynamics information on proteins at an atomic level [13,14].…”

Section: Introductionmentioning

confidence: 99%

Dynamics study on the stability of animal prion proteins

Chen¹,

Duan²,

Zhu³

et al. 2014

Turk J Bioch

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“…Some MD researches have reported the behavior of insulin monomer, dimer and hexamer in solvent [9][10][11][12]. Since the calculation amount is large for considering the all-atom interactions and solving Newtonian equations, the limited number of trajectories is often computed in those MD simulations.…”

Section: Introductionmentioning

confidence: 99%

“…Our study employed the structure of T 6 human insulin with 1.0 Å resolution determined by cryo-EM (PDB entry: 1mso) [1]. Its B chain contains two helix (residues [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] and an extended C-terminal structure (residues 24-26).…”

Section: Introductionmentioning

confidence: 99%

Conformational Ensemble of B Chain in T₆ Human Insulin Based on the Landau Free Energy

Lei

Liu

et al. 2018

Acta Phys. Pol. A

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Insulin is an important peptide hormone for the glucose metabolism. The structural flexibility of insulin B chain attracts a lot of our attention for understanding the biological activity. Our work carried out the extensive sampling to statistically clarify the structural changes of isolated T6 human insulin B chain. We introduced the Landau free energy to describe the isolated insulin B chain whose experimental structure locates a local energy minimum. Its trained model was subjected to thousands of heating and cooling circles between the high and low temperatures. Six typical structure clusters were found by classifying the final generated structures with RMSD and radius of gyration. The structures in clusters indicate the potential deformations of insulin B chain at residues 5-8 of N-terminus, residues 9-12 of central helix and residues 24-29 of C-terminus, which agrees with the experimental results.

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Protein flexibility: Multiple molecular dynamics simulations of insulin chain B

Cited by 56 publications

References 63 publications

Variability of the Cyclin-Dependent Kinase 2 Flexibility Without Significant Change in the Initial Conformation of the Protein or Its Environment; a Computational Study

Variability of the Cyclin-Dependent Kinase 2 Flexibility Without Significant Change in the Initial Conformation of the Protein or Its Environment; a Computational Study

Dynamics study on the stability of animal prion proteins

Conformational Ensemble of B Chain in T₆ Human Insulin Based on the Landau Free Energy

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Protein flexibility: Multiple molecular dynamics simulations of insulin chain B

Cited by 56 publications

References 63 publications

Variability of the Cyclin-Dependent Kinase 2 Flexibility Without Significant Change in the Initial Conformation of the Protein or Its Environment; a Computational Study

Variability of the Cyclin-Dependent Kinase 2 Flexibility Without Significant Change in the Initial Conformation of the Protein or Its Environment; a Computational Study

Dynamics study on the stability of animal prion proteins

Conformational Ensemble of B Chain in T6 Human Insulin Based on the Landau Free Energy

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Conformational Ensemble of B Chain in T₆ Human Insulin Based on the Landau Free Energy