The role of hydrogen bonds in protein-ligand interactions. DFT calculations in 1,3-dihydrobenzimidazole-2 thione derivatives with glycinamide as model HIV RT inhibitors

2011 ◽  
Vol 112 (7) ◽  
pp. 1786-1795 ◽  
Author(s):  
Robert Kretschmer ◽  
Daniel Kinzel ◽  
Leticia González
Keyword(s):  
Hydrogen Bonds ◽  
Dft Calculations ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Hiv Rt ◽  
Rt Inhibitors

scholarly journals Halogen Bonding: An Underestimated Player in Membrane–drug Interactions

2020 ◽  
Author(s):  
Rafael Nunes ◽  
Diogo Vila Viçosa ◽  
Paulo J. Costa
Keyword(s):  
Drug Discovery ◽  
Chemical Space ◽  
Noncovalent Interactions ◽  
Halogen Bonding ◽  
Lewis Bases ◽  
Protein Ligand Interactions ◽  
Biochemical Systems ◽  
Ligand Interactions ◽  
Dynamics Simulations

<div>Halogen bonds (HaBs) are noncovalent interactions where halogen atoms act as electrophilic species interacting with Lewis bases. These interactions are relevant in biochemical systems being increasingly explored in drug discovery, mainly to modulate protein–ligand interactions. In this work, we report evidence for the existence of HaB-mediated halogen–phospholipid recognition phenomena as our molecular dynamics simulations support the existence of favorable interactions between halobenzene derivatives and both phosphate (PO) or ester (CO) oxygen acceptors from model phospholipid bilayers, thus providing insights into the role of HaBs in driving the permeation of halogenated drug like molecules across biological membranes. This represents a relevant molecular mechanism, previously overlooked, determining the pharmacological activity of halogenated molecules with implications in drug discovery and development, a place where halogenated molecules account for a significant part of the chemical space. Our data also shows that, as the ubiquitous hydrogen bond, HaBs should be accounted for in the development of membrane permeability models.</div>

On the Role of Flexibility in Protein-Ligand Interactions: the Example of p53 Tetramerization Domain

2011 ◽  
Vol 6 (6) ◽  
pp. 1463-1469 ◽  
Author(s):  
Susana Gordo ◽  
Vera Martos ◽  
Marta Vilaseca ◽  
Margarita Menéndez ◽  
Javier de Mendoza ◽  
...  
Keyword(s):  
Protein Ligand Interactions ◽  
Tetramerization Domain ◽  
Ligand Interactions

scholarly journals Molecular basis for high affinity agonist binding in GPCRs

2018 ◽  
Author(s):  
Tony Warne ◽  
Patricia C. Edwards ◽  
Andrew S. Doré ◽  
Andrew G. W. Leslie ◽  
Christopher G. Tate
Keyword(s):  
Hydrogen Bonds ◽  
Binding Site ◽  
G Protein ◽  
Molecular Basis ◽  
Agonist Binding ◽  
High Affinity ◽  
Protein Ligand Interactions ◽  
Wide Range ◽  
Ligand Interactions ◽  
G Protein Coupled

AbstractA characteristic of GPCRs in the G protein-coupled state is that the affinity of the agonist often increases significantly, but the molecular basis for this is unclear. We have determined six active-state structures of the β1-adrenoceptor (β1AR) bound to conformation-specific nanobodies in the presence of agonists of varying efficacy. A direct comparison with structures of β1AR in inactive states bound to the identical ligands showed a 24-42% reduction in the volume of the orthosteric binding site. Potential hydrogen bonds were also shorter, and there was up to a 30% increase in the number of atomic contacts between the receptor and ligand. GPCRs are highly conserved, so these factors will likely be essential in increasing the affinity of a wide range of structurally distinct agonists.One Sentence SummaryHigh affinity agonist binding to G protein-coupled GPCRs results from an increase in the number and strength of protein-ligand interactions.

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