POSITIONING OF Ftz–F1 DOMAIN AFFECTS ON THE ACTIVITY OF HUMAN LRH-1: MOLECULAR DYNAMICS STUDY ON HUMAN LRH-1-DNA COMPLEXES

2012 ◽  
Vol 11 (02) ◽  
pp. 329-359 ◽  
Author(s):  
SHUAI LI ◽  
LEI WU ◽  
HUI YU ◽  
XUEFENG GAO ◽  
ZHENGQIANG LI ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Helical Axis ◽  
Wild Type ◽  
Triple Mutant ◽  
Base Pairs ◽  
Dna Complexes ◽  
Protein Dna Interactions ◽  
Dynamics Simulations ◽  
Mutant Forms ◽  
Helical Parameters

Molecular dynamics simulations for hLRH-1 (human liver receptor homologue-1) — DNA complexes were to investigate how the Ftz-F1 domain to regulate the transcriptional activity of hLRH-1. Comparative analyses of the three MD trajectories of hLRH-1 complexes suggest that the differential transcriptional activities of the wild-type hLRH-1, double-mutant and triple-mutant are due to alterative protein-DNA interactions. Further, the changes of position of Ftz–F1 domain can only exert limited effects on structures of the DBD (DNA binding domain), while the differences in the bound DNA's bending angles and helical parameters of key base pairs in the three systems result from the altering in distributions of the electrostatic potential surface, which varies with the positioning between the Ftz–F1 and the DBD. The disruptions or weakening of key interactions on several base pairs in the core sequence are mainly due to their distinct displacements from the helical axis in the mutant forms. So the Ftz-F1 domain can regulate the activity of the hLRH-1 by influencing conformations of the bound DNA.

Molecular dynamics simulations reveal structural differences among wild-type NPC1 protein and its mutant forms

2019 ◽  
Vol 38 (12) ◽  
pp. 3527-3532 ◽  
Author(s):  
M. Martínez-Archundia ◽  
T. G. Hernández Mojica ◽  
J. Correa-Basurto ◽  
S. Montaño ◽  
A. Camacho-Molina
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Wild Type ◽  
Structural Differences ◽  
Dynamics Simulations ◽  
Mutant Forms

scholarly journals Dynamics and Thermodynamics of Transthyretin Association from Molecular Dynamics Simulations

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Cedrix J. Dongmo Foumthuim ◽  
Alessandra Corazza ◽  
Rodolfo Berni ◽  
Gennaro Esposito ◽  
Federico Fogolari
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Energy Analysis ◽  
Wild Type ◽  
Triple Mutant ◽  
Energy Functions ◽  
Dimer Interface ◽  
Dynamics Simulations ◽  
Free Energy Analysis ◽  
Effective Energy Functions

Molecular dynamics simulations are used in this work to probe the structural stability and the dynamics of engineered mutants of transthyretin (TTR), i.e., the double mutant F87M/L110M (MT-TTR) and the triple mutant F87M/L110M/S117E (3M-TTR), in relation to wild-type. Free energy analysis from end-point simulations and statistical effective energy functions are used to analyze trajectories, revealing that mutations do not have major impact on protein structure but rather on protein association, shifting the equilibria towards dissociated species. The result is confirmed by the analysis of 3M-TTR which shows dissociation within the first 10 ns of the simulation, indicating that contacts are lost at the dimer-dimer interface, whereas dimers (formed by monomers which pair to form two extended β-sheets) appear fairly stable. Overall the simulations provide a detailed view of the dynamics and thermodynamics of wild-type and mutant transthyretins and a rationale of the observed effects.

scholarly journals Exploration of the cofactor specificity of wild-type phosphite dehydrogenase and its mutant using molecular dynamics simulations

RSC Advances ◽  
2021 ◽  
Vol 11 (24) ◽  
pp. 14527-14533
Author(s):  
Kunlu Liu ◽  
Min Wang ◽  
Yubo Zhou ◽  
Hongxiang Wang ◽  
Yudong Liu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Wild Type ◽  
Cofactor Specificity ◽  
Phosphite Dehydrogenase ◽  
Dynamics Simulations

Phosphite dehydrogenase (Pdh) catalyzes the NAD-dependent oxidation of phosphite to phosphate with the formation of NADH.

Observation of “Ionic Lock” Formation in Molecular Dynamics Simulations of Wild-Type β1and β2Adrenergic Receptors

Biochemistry ◽  
2009 ◽  
Vol 48 (22) ◽  
pp. 4789-4797 ◽  
Author(s):  
Stefano Vanni ◽  
Marilisa Neri ◽  
Ivano Tavernelli ◽  
Ursula Rothlisberger
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Wild Type ◽  
Dynamics Simulations

scholarly journals On the dynamics of some small structural motifs in rRNA upon ligand binding

2008 ◽  
Vol 73 (1) ◽  
pp. 41-53
Author(s):  
Aleksandra Rakic ◽  
Petar Mitrasinovic
Keyword(s):  
Molecular Dynamics ◽  
Conformational Changes ◽  
Binding Sites ◽  
De Novo ◽  
Reference Structure ◽  
Base Pairs ◽  
Rna Sequences ◽  
Conformational Model ◽  
Thermodynamic Variables ◽  
Dynamics Simulations

The present study characterizes using molecular dynamics simulations the behavior of the GAA (1186-1188) hairpin triloops with their closing c-g base pairs in large ribonucleoligand complexes (PDB IDs: 1njn, 1nwy, 1jzx). The relative energies of the motifs in the complexes with respect to that in the reference structure (unbound form of rRNA; PDB ID: 1njp) display the trends that agree with those of the conformational parameters reported in a previous study1 utilizing the de novo pseudotorsional (?,?) approach. The RNA regions around the actual RNA-ligand contacts, which experience the most substantial conformational changes upon formation of the complexes were identified. The thermodynamic parameters, based on a two-state conformational model of RNA sequences containing 15, 21 and 27 nucleotides in the immediate vicinity of the particular binding sites, were evaluated. From a more structural standpoint, the strain of a triloop, being far from the specific contacts and interacting primarily with other parts of the ribosome, was established as a structural feature which conforms to the trend of the average values of the thermodynamic variables corresponding to the three motifs defined by the 15-, 21- and 27-nucleotide sequences. From a more functional standpoint, RNA-ligand recognition is suggested to be presumably dictated by the types of ligands in the complexes.

scholarly journals Molecular dynamics simulations of the interaction of wild type and mutant human CYP2J2 with polyunsaturated fatty acids

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
K. K. Abelak ◽  
D. Bishop-Bailey ◽  
I. Nobeli
Keyword(s):  
Molecular Dynamics ◽  
Arachidonic Acid ◽  
Molecular Dynamics Simulations ◽  
Molecular Mechanisms ◽  
Homology Model ◽  
Cytochrome P450 Enzyme ◽  
Wild Type ◽  
Substrate Preferences ◽  
P450 Enzyme ◽  
Dynamics Simulations

Abstract Objectives The data presented here is part of a study that was aimed at characterizing the molecular mechanisms of polyunsaturated fatty acid metabolism by CYP2J2, the main cytochrome P450 enzyme active in the human cardiovasculature. This part comprises the molecular dynamics simulations of the binding of three eicosanoid substrates to wild type and mutant forms of the enzyme. These simulations were carried out with the aim of dissecting the importance of individual residues in the active site and the roles they might play in dictating the binding and catalytic specificity exhibited by CYP2J2. Data description The data comprise: (a) a new homology model of CYP2J2, (b) a number of predicted low-energy complexes of CYP2J2 with arachidonic acid, docosahexaenoic acid and eicosapentaenoic acid, produced with molecular docking and (c) a series of molecular dynamics simulations of the wild type and four mutants interacting with arachidonic acid as well as simulations of the wild type interacting with the two other eicosanoid ligands. The simulations may be helpful in identifying the determinants of substrate specificity of this enzyme and in unraveling the role of individual mutations on its function. They may also help guide the generation of mutants with altered substrate preferences.

Sign in / Sign up

Export Citation Format

Share Document