Molecular Recognition of Protein−Ligand Complexes:  Applications to Drug Design

1997 ◽  
Vol 97 (5) ◽  
pp. 1359-1472 ◽  
Author(s):  
Robert E. Babine ◽  
Steven L. Bender
Keyword(s):  
Molecular Recognition ◽  
Drug Design

Advances in the molecular recognition of DNA — A step towards therapeutic drug design

1995 ◽  
Vol 23 (2) ◽  
pp. 56-64 ◽  
Author(s):  
Arvind M. Kayastha ◽  
Prakash Prabhakar ◽  
O.P. Malhotra
Keyword(s):  
Molecular Recognition ◽  
Drug Design ◽  
Therapeutic Drug

Advances in Theoretical Studies on the Design of Single Boron Atom Compounds

2018 ◽  
Vol 24 (29) ◽  
pp. 3466-3475 ◽  
Author(s):  
Martiniano Bello
Keyword(s):  
Molecular Recognition ◽  
Drug Design ◽  
Boron Atom ◽  
Force Fields ◽  
Covalent Binding ◽  
Binding Modes ◽  
In Silico Studies ◽  
Reversible Covalent ◽  
The Individual ◽  
Insight Into

Background: Single Boron Atom Compounds (SBACs) have been used for drug discovery in diseaseassociated proteins due to the empty p-orbital in the atomic structure of boron, which allows it to experience diverse binding modes during molecular recognition with a range of proteins. Objective: During the molecular recognition process with a protein target, SBACs can assume an anionic tetragonal arrangement or a neutral trigonal planar structure to produce four possible reversible covalent or non-covalent binding modes with a protein. However, the development of new SBACs has been hampered by the fact that most of the force fields present in many of the software packages used in drug design lack the various types of boron atom parameters. Methods: We review in silico studies in which a series of theory-based computational strategies have been used to overcome the lack of boron parameters in most of the force fields used in drug design. Results: The modeling studies discussed in this review have provided substantial insight into the molecular recognition of SBACs targeting different receptors, including the elucidation of some of the key interactions, which serve as a guide for the development of selective SBACs. Conclusion: Although the strategies employed in many of the studies presented here should serve in the development of selective SBACs, it is clear that the development of the precise force field parameters, which include not only the individual atom types but also the entire molecule, is still lacking, yet it is a necessary requirement for the design of new SBACS as well as for gaining insight into their molecular recognition.

scholarly journals Molecular recognition of ternary complexes: a new dimension in the structure-guided design of chemical degraders

2017 ◽  
Vol 61 (5) ◽  
pp. 505-516 ◽  
Author(s):  
Scott J. Hughes ◽  
Alessio Ciulli
Keyword(s):  
Molecular Recognition ◽  
Drug Design ◽  
Protein Interactions ◽  
Protein Complexes ◽  
Structural Data ◽  
Ternary Complexes ◽  
Protein Protein Interactions ◽  
New Paradigm ◽  
Design And Optimization ◽  
Three Body

Molecular glues and bivalent inducers of protein degradation (also known as PROTACs) represent a fascinating new modality in pharmacotherapeutics: the potential to knockdown previously thought ‘undruggable’ targets at sub-stoichiometric concentrations in ways not possible using conventional inhibitors. Mounting evidence suggests these chemical agents, in concert with their target proteins, can be modelled as three-body binding equilibria that can exhibit significant cooperativity as a result of specific ligand-induced molecular recognition. Despite this, many existing drug design and optimization regimens still fixate on binary target engagement, in part due to limited structural data on ternary complexes. Recent crystal structures of protein complexes mediated by degrader molecules, including the first PROTAC ternary complex, underscore the importance of protein–protein interactions and intramolecular contacts to the mode of action of this class of compounds. These discoveries have opened the door to a new paradigm for structure-guided drug design: borrowing surface area and molecular recognition from nature to elicit cellular signalling.

Role of Aromatic Rings in the Molecular Recognition of Aminoglycoside Antibiotics: Implications for Drug Design

2010 ◽  
Vol 132 (34) ◽  
pp. 12074-12090 ◽  
Author(s):  
Tatiana Vacas ◽  
Francisco Corzana ◽  
Gonzalo Jiménez-Osés ◽  
Carlos González ◽  
Ana M. Gómez ◽  
...  
Keyword(s):  
Molecular Recognition ◽  
Drug Design ◽  
Aminoglycoside Antibiotics ◽  
Aromatic Rings
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