Only Subtle Protein Conformational Adaptations Are Required for Ligand Binding to Thyroid Hormone Receptors: Simulations Using a Novel Multipoint Steered Molecular Dynamics Approach

2008 ◽  
Vol 112 (34) ◽  
pp. 10741-10751 ◽  
Author(s):  
Leandro Martínez ◽  
Igor Polikarpov ◽  
Munir S. Skaf
Keyword(s):  
Molecular Dynamics ◽  
Thyroid Hormone ◽  
Ligand Binding ◽  
Hormone Receptors ◽  
Steered Molecular Dynamics ◽  
Thyroid Hormone Receptors

scholarly journals Constant velocity pulling and unfolding of thyroid hormone receptor by steered molecular dynamics

BIBECHANA ◽  
2020 ◽  
Vol 17 ◽  
pp. 50-57
Author(s):  
Tika Ram Lamichhane ◽  
Hari Prasad Lamichhane
Keyword(s):  
Molecular Dynamics ◽  
Thyroid Hormone ◽  
Ligand Binding ◽  
Hormone Receptor ◽  
Constant Velocity ◽  
Thyroid Hormone Receptor ◽  
Steered Molecular Dynamics ◽  
Electrostatic Energy ◽  
Gene Expressions ◽  
Globular Form

Unfolding pathways of T3 liganded thyroid hormone receptor (THRT3) can be studied by using the protocols of steered molecular dynamics (SMD). Theory of constant velocity pulling has been implemented to the structure of THRT3 in a neutral water-ion solution equilibrated up to 20 ns. The globular form of THRT3 is completely unfolded extending N-C termini from 38 Å to 876 Å at a constant speed of 0.1 Å/ps by means of 8.5 ns long SMD simulations. The peak force measured in the intermediate conformations is related to a burst of backbone H-bonds among a-helices and b-hairpins. With decrease in H-bonds, electrostatic energy increases by losing gradually the secondary structure and separating a and b-strands in solution. The force at the end (t > 8.5 ns) increases steeply with the large increase in bond-angle and bond-length potentials when the system becomes completely unfolded. The hydrophobic ligand binding domain (LBD) of THR-b with load bearing H-bonds protects T3 from water attack.  Even after complete unfolding of THR-b LBD, the position of T3 is not deviated more than 2.5 Å and a large number of water molecules remain in the surrounding of this domain area. This is a strong evidence for the mechanochemical stability of a receptor protein’s LBD towards hormone activated gene expressions followed by ligand binding and dissociation. BIBECHANA 17 (2020) 50-57

scholarly journals Molecular Dynamics Simulations Reveal Multiple Pathways of Ligand Dissociation from Thyroid Hormone Receptors

2005 ◽  
Vol 89 (3) ◽  
pp. 2011-2023 ◽  
Author(s):  
Leandro Martínez ◽  
Milton T. Sonoda ◽  
Paul Webb ◽  
John D. Baxter ◽  
Munir S. Skaf ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Thyroid Hormone ◽  
Molecular Dynamics Simulations ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptors ◽  
Ligand Dissociation ◽  
Dynamics Simulations

On the Denaturation Mechanisms of the Ligand Binding Domain of Thyroid Hormone Receptors

2010 ◽  
Vol 114 (3) ◽  
pp. 1529-1540 ◽  
Author(s):  
Leandro Martínez ◽  
Paulo C. T. Souza ◽  
Wanius Garcia ◽  
Fernanda A. H. Batista ◽  
Rodrigo V. Portugal ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Ligand Binding ◽  
Hormone Receptors ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Thyroid Hormone Receptors
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