Theoretical study of iron-ligand binding: mechanism of ferrocene formation from iron plus cyclopentadiene

1992 ◽  
Vol 96 (4) ◽  
pp. 1683-1690 ◽  
Author(s):  
Michael L. McKee
Keyword(s):  
Ligand Binding ◽  
Theoretical Study ◽  
Binding Mechanism

scholarly journals Cryptic-site binding mechanism of medium-sized Bcl-xL inhibiting compounds elucidated by McMD-based dynamic docking simulations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gert-Jan Bekker ◽  
Ikuo Fukuda ◽  
Junichi Higo ◽  
Yoshifumi Fukunishi ◽  
Narutoshi Kamiya
Keyword(s):  
Ligand Binding ◽  
Cancer Progression ◽  
Hydrophobic Interactions ◽  
Binding Mechanism ◽  
Docking Simulations ◽  
Large Conformational Change ◽  
Binding Pockets ◽  
Dynamic Docking ◽  
Site Binding ◽  
Apo State

AbstractWe have performed multicanonical molecular dynamics (McMD) based dynamic docking simulations to study and compare the binding mechanism between two medium-sized inhibitors (ABT-737 and WEHI-539) that bind to the cryptic site of Bcl-xL, by exhaustively sampling the conformational and configurational space. Cryptic sites are binding pockets that are transiently formed in the apo state or are induced upon ligand binding. Bcl-xL, a pro-survival protein involved in cancer progression, is known to have a cryptic site, whereby the shape of the pocket depends on which ligand is bound to it. Starting from the apo-structure, we have performed two independent McMD-based dynamic docking simulations for each ligand, and were able to obtain near-native complex structures in both cases. In addition, we have also studied their interactions along their respective binding pathways by using path sampling simulations, which showed that the ligands form stable binding configurations via predominantly hydrophobic interactions. Although the protein started from the apo state, both ligands modulated the pocket in different ways, shifting the conformational preference of the sub-pockets of Bcl-xL. We demonstrate that McMD-based dynamic docking is a powerful tool that can be effectively used to study binding mechanisms involving a cryptic site, where ligand binding requires a large conformational change in the protein to occur.

scholarly journals Ligand binding mechanism of β-lactoglobulin

1999 ◽  
Vol 39 (supplement) ◽  
pp. S118
Author(s):  
M. Taguchi ◽  
M Hoshino ◽  
S. Aimoto ◽  
Y. Goto
Keyword(s):  
Ligand Binding ◽  
Binding Mechanism ◽  
Β Lactoglobulin

scholarly journals Combinatorial peptide libraries reveal the ligand-binding mechanism of the oligopeptide receptor OppA of Lactococcus lactis

2000 ◽  
Vol 97 (23) ◽  
pp. 12487-12492 ◽  
Author(s):  
F. J. M. Detmers ◽  
F. C. Lanfermeijer ◽  
R. Abele ◽  
R. W. Jack ◽  
R. Tampe ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Lactococcus Lactis ◽  
Peptide Libraries ◽  
Binding Mechanism ◽  
Combinatorial Peptide Libraries

scholarly journals Electrostatic Tuning of the Ligand Binding Mechanism by Glu27 in Nitrophorin 7

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Stefania Abbruzzetti ◽  
Alessandro Allegri ◽  
Axel Bidon-Chanal ◽  
Hideaki Ogata ◽  
Giancarlo Soavi ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Binding Mechanism

scholarly journals Multiscale simulations examining glycan shield effects on drug binding to influenza neuraminidase

2020 ◽  
Author(s):  
Christian Seitz ◽  
Lorenzo Casalino ◽  
Robert Konecny ◽  
Gary Huber ◽  
Rommie E. Amaro ◽  
...  
Keyword(s):  
Drug Development ◽  
Ligand Binding ◽  
Binding Site ◽  
Brownian Dynamics ◽  
Drug Binding ◽  
Binding Mechanism ◽  
Drug Effectiveness ◽  
Future Drug ◽  
Dynamics Simulations ◽  
Inhibit Antibody

AbstractInfluenza neuraminidase is an important drug target. Glycans are present on neuraminidase, and are generally considered to inhibit antibody binding via their glycan shield. In this work we studied the effect of glycans on the binding kinetics of antiviral drugs to the influenza neuraminidase. We created all-atom in silico systems of influenza neuraminidase with experimentally-derived glycoprofiles consisting of four systems with different glycan conformations and one system without glycans. Using Brownian dynamics simulations, we observe a two- to eight-fold decrease in the rate of ligand binding to the primary binding site of neuraminidase due to the presence of glycans. These glycans are capable of covering much of the surface area of neuraminidase, and the ligand binding inhibition is derived from glycans sterically occluding the primary binding site on a neighboring monomer. Our work also indicates that drugs preferentially bind to the primary binding site (i.e. the active site) over the secondary binding site, and we propose a binding mechanism illustrating this. These results help illuminate the complex interplay between glycans and ligand binding on the influenza membrane protein neuraminidase.Statement of SignificanceThe influenza glycoprotein neuraminidase is the target for three FDA-approved influenza drugs in the US. However, drug resistance and low drug effectiveness merits further drug development towards neuraminidase, which is hindered by our limited understanding of glycan effects on ligand binding. Generally, drug developers do not include glycans in their development pipelines. Here, we show that even though glycans can reduce drug binding towards neuraminidase, we recommend future drug development work to focus on strong binders with a long lifetime. Furthermore, we examine the binding competition between the primary and secondary binding sites on neuraminidase, leading us to propose a new, to the best of our knowledge, multivalent binding mechanism.

Conformational Trapping of a β-Glucosides-Binding Protein Unveils the Selective Two-Step Ligand-Binding Mechanism of ABC Importers

2020 ◽  
Vol 432 (20) ◽  
pp. 5711-5734
Author(s):  
Monika Chandravanshi ◽  
Reshama Samanta ◽  
Shankar Prasad Kanaujia
Keyword(s):  
Ligand Binding ◽  
Binding Protein ◽  
Binding Mechanism

scholarly journals Exploring the PXR ligand binding mechanism with advanced Molecular Dynamics methods

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Stefano Motta ◽  
Lara Callea ◽  
Sara Giani Tagliabue ◽  
Laura Bonati
Keyword(s):  
Molecular Dynamics ◽  
Ligand Binding ◽  
Binding Mechanism ◽  
Molecular Dynamics Methods

scholarly journals Evidence for the “Dock, Lock, and Latch” Ligand Binding Mechanism of the Staphylococcal Microbial Surface Component Recognizing Adhesive Matrix Molecules (MSCRAMM) SdrG

2007 ◽  
Vol 283 (1) ◽  
pp. 638-647 ◽  
Author(s):  
M. Gabriela Bowden ◽  
Alejandro P. Heuck ◽  
Karthe Ponnuraj ◽  
Elena Kolosova ◽  
Damon Choe ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Binding Mechanism ◽  
Adhesive Matrix ◽  
Surface Component

Oxidatively Induced Reactivity of [Fe2(CO)4(κ2-dppe)(μ-pdt)]: an Electrochemical and Theoretical Study of the Structure Change and Ligand Binding Processes

2011 ◽  
Vol 50 (24) ◽  
pp. 12575-12585 ◽  
Author(s):  
Dounia Chouffai ◽  
Giuseppe Zampella ◽  
Jean-François Capon ◽  
Luca De Gioia ◽  
Frédéric Gloaguen ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Theoretical Study ◽  
Structure Change
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