scholarly journals Effect of the Arg456His mutation on the three-dimensional structure of cytochrome P450 1A2 predicted by molecular dynamics simulations

2018 ◽  
Vol 1136 ◽  
pp. 012023
Author(s):  
Y Watanabe ◽  
K Kato ◽  
S Fukuyoshi ◽  
M Hiratsuka ◽  
N Yamaotsu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Cytochrome P450 ◽  
Molecular Dynamics Simulations ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Cytochrome P450 1A2 ◽  
Three Dimensional Structure ◽  
Dynamics Simulations

scholarly journals Conformational Ensembles of Non-Coding Elements in the SARS-CoV-2 Genome from Molecular Dynamics Simulations

2020 ◽  
Author(s):  
Sandro Bottaro ◽  
Giovanni Bussi ◽  
Kresten Lindorff-Larsen
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Three Dimensional ◽  
Genomic Region ◽  
Dimensional Structure ◽  
Structure Based Drug Design ◽  
Stem Loop ◽  
Rna Molecules ◽  
Conformational Ensembles ◽  
Dynamics Simulations

The 5' untranslated region (UTR) of SARS-CoV-2 genome is a conserved, functional and structured genomic region consisting of several RNA stem-loop elements. While the secondary structure of such elements has been determined experimentally, their three-dimensional structure is not known yet. Here, we predict structure and dynamics of five RNA stem-loops in the 5'-UTR of SARS-CoV-2 by extensive atomistic molecular dynamics simulations, more than 0.5ms of aggregate simulation time, in combination with enhanced sampling techniques. We compare simulations with available experimental data, describe the resulting conformational ensembles, and identify the presence of specific structural rearrengements in apical and internal loops that may be functionally relevant. Our atomic-detailed structural predictions reveal a rich dynamics in these RNA molecules, could help the experimental characterisation of these systems, and provide putative three-dimensional models for structure-based drug design studies.

Molecular modelling studies of sirtuin 2 inhibitors using three-dimensional structure–activity relationship analysis and molecular dynamics simulations

2015 ◽  
Vol 11 (3) ◽  
pp. 723-733 ◽  
Author(s):  
Yu-Chung Chuang ◽  
Ching-Hsun Chang ◽  
Jen-Tai Lin ◽  
Chia-Ning Yang
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Comfa Model ◽  
Relationship Analysis ◽  
Structure Activity ◽  
Molecular Modelling Studies ◽  
Modelling Studies ◽  
Dynamics Simulations

In this work, a CoMFA model and molecular dynamics simulations provide guidelines for drug development of SIRT2 inhibitors.

scholarly journals Deciphering Structural Alterations Associated with Activity Reductions of Genetic Polymorphisms in Cytochrome P450 2A6 Using Molecular Dynamics Simulations

2021 ◽  
Vol 22 (18) ◽  
pp. 10119
Author(s):  
Koichi Kato ◽  
Tomoki Nakayoshi ◽  
Rika Nokura ◽  
Hiroki Hosono ◽  
Masahiro Hiratsuka ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Cytochrome P450 ◽  
Molecular Dynamics Simulations ◽  
Genetic Polymorphisms ◽  
Structural Changes ◽  
Three Dimensional ◽  
Smoking Behavior ◽  
Enzymatic Activities ◽  
Access Channel ◽  
Dynamics Simulations

Cytochrome P450 (CYP) 2A6 is a monooxygenase involved in the metabolism of various endogenous and exogenous chemicals, such as nicotine and therapeutic drugs. The genetic polymorphisms in CYP2A6 are a cause of individual variation in smoking behavior and drug toxicities. The enzymatic activities of the allelic variants of CYP2A6 were analyzed in previous studies. However, the three-dimensional structures of the mutants were not investigated, and the mechanisms underlying activity reduction remain unknown. In this study, to investigate the structural changes involved in the reduction in enzymatic activities, we performed molecular dynamics simulations for ten allelic mutants of CYP2A6. For the calculated wild type structure, no significant structural changes were observed in comparison with the experimental structure. On the other hand, the mutations affected the interaction with heme, substrates, and the redox partner. In CYP2A6.44, a structural change in the substrate access channel was also observed. Those structural effects could explain the alteration of enzymatic activity caused by the mutations. The results of simulations provide useful information regarding the relationship between genotype and phenotype.

scholarly journals Lipid molecules can induce an opening of membrane-facing tunnels in cytochrome P450 1A2

2016 ◽  
Vol 18 (44) ◽  
pp. 30344-30356 ◽  
Author(s):  
Petr Jeřábek ◽  
Jan Florián ◽  
Václav Martínek
Keyword(s):  
Molecular Dynamics ◽  
Aqueous Solution ◽  
Cytochrome P450 ◽  
Molecular Dynamics Simulations ◽  
Coarse Grained ◽  
Cytochrome P450 1A2 ◽  
Structure And Dynamics ◽  
Human Cytochrome ◽  
Membrane Bound ◽  
Dynamics Simulations

The structure and dynamics of the membrane-bound full-length human cytochrome P450 1A2 (CYP1A2) in aqueous solution determined by coarse-grained and all-atom molecular dynamics simulations.

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