Conformational changes of peptidoglycan fragments during their interactions with vancomycin

AbstractSix complexes of vancomycin and peptidoglycan precursors were studied via molecular dynamics simulations. The interactions between the antibiotic and peptidoglycan fragments were identified and described in detail. All six studied modifications of the peptidoglycan precursor resulted in a weakening of the interaction with vancomycin when comparing to the native D-Ala-D-Ala-terminated fragment. It was confirmed that the N-terminus of the vancomycin is directly responsible for peptidoglycan recognition and antimicrobial activity. In simulated systems, the saccharide part of the antibiotic interacts with peptide precursors, thus it could also be important for antimicrobial activity. The complex terminated with D-Lac is the only one in which there is a weak interaction with the sugar moiety in the simulated systems. Analysis of conformational changes is a major scope of this work. The lack of interactions resulting from modification of the peptidoglycan precursors (D-Lac, D-Ser or other substitution) would be counterbalanced by proper modifications of the vancomycin moiety, especially the saccharide part of vancomycin.

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Molecular Basis of Glucose Transport Mechanism in Plants

10.26434/chemrxiv.8049848.v1 ◽

2019 ◽

Cited By ~ 2

Author(s):

Balaji Selvam ◽

Ya-Chi Yu ◽

Liqing Chen ◽

Diwakar Shukla

Keyword(s):

Molecular Dynamics ◽

Free Energy ◽

Molecular Dynamics Simulations ◽

Conformational Changes ◽

Transport Mechanism ◽

Conformational Dynamics ◽

Site Directed Mutagenesis ◽

Free Energy Barrier ◽

Transport Cycle ◽

Dynamics Simulations

<p>The SWEET family belongs to a class of transporters in plants that undergoes large conformational changes to facilitate transport of sugar molecules across the cell membrane. However, the structures of their functionally relevant conformational states in the transport cycle have not been reported. In this study, we have characterized the conformational dynamics and complete transport cycle of glucose in OsSWEET2b transporter using extensive molecular dynamics simulations. Using Markov state models, we estimated the free energy barrier associated with different states as well as 1 for the glucose the transport mechanism. SWEETs undergoes structural transition to outward-facing (OF), Occluded (OC) and inward-facing (IF) and strongly support alternate access transport mechanism. The glucose diffuses freely from outside to inside the cell without causing major conformational changes which means that the conformations of glucose unbound and bound snapshots are exactly same for OF, OC and IF states. We identified a network of hydrophobic core residues at the center of the transporter that restricts the glucose entry to the cytoplasmic side and act as an intracellular hydrophobic gate. The mechanistic predictions from molecular dynamics simulations are validated using site-directed mutagenesis experiments. Our simulation also revealed hourglass like intermediate states making the pore radius narrower at the center. This work provides new fundamental insights into how substrate-transporter interactions actively change the free energy landscape of the transport cycle to facilitate enhanced transport activity.</p>

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Molecular mechanism concerning conformational changes of CDK2 mediated by binding of inhibitors using molecular dynamics simulations and principal component analysis

SAR and QSAR in Environmental Research ◽

10.1080/1062936x.2021.1934896 ◽

2021 ◽

pp. 1-22

Author(s):

S.S. Liang ◽

X.G. Liu ◽

Y.X. Cui ◽

S.L. Zhang ◽

Q.G. Zhang ◽

...

Keyword(s):

Molecular Dynamics ◽

Principal Component Analysis ◽

Molecular Dynamics Simulations ◽

Molecular Mechanism ◽

Conformational Changes ◽

Principal Component ◽

Component Analysis ◽

Dynamics Simulations

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Studies of Conformational Changes of Tubulin Induced by Interaction with Kinesin Using Atomistic Molecular Dynamics Simulations

International Journal of Molecular Sciences ◽

10.3390/ijms22136709 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6709

Author(s):

Xiao-Xuan Shi ◽

Peng-Ye Wang ◽

Hong Chen ◽

Ping Xie

Keyword(s):

Molecular Dynamics ◽

High Resolution ◽

Binding Energy ◽

Molecular Dynamics Simulations ◽

Conformational Changes ◽

Weak Interactions ◽

Molecular Motor ◽

Structural Data ◽

Calculated Binding Energy ◽

Dynamics Simulations

The transition between strong and weak interactions of the kinesin head with the microtubule, which is regulated by the change of the nucleotide state of the head, is indispensable for the processive motion of the kinesin molecular motor on the microtubule. Here, using all-atom molecular dynamics simulations, the interactions between the kinesin head and tubulin are studied on the basis of the available high-resolution structural data. We found that the strong interaction can induce rapid large conformational changes of the tubulin, whereas the weak interaction cannot. Furthermore, we found that the large conformational changes of the tubulin have a significant effect on the interaction of the tubulin with the head in the weak-microtubule-binding ADP state. The calculated binding energy of the ADP-bound head to the tubulin with the large conformational changes is only about half that of the tubulin without the conformational changes.

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