Use of secondary structure element information in drug design: polypharmacology and conserved motifs in protein–ligand binding and protein–protein interfaces

2011 ◽  
Vol 3 (6) ◽  
pp. 699-708 ◽  
Author(s):  
Oliver Koch
Keyword(s):  
Secondary Structure ◽  
Drug Design ◽  
Ligand Binding ◽  
Secondary Structure Element ◽  
Conserved Motifs ◽  
Protein Interfaces

Computational Biology Tools for Identifying Specific Ligand Binding Residues for Novel Agrochemical and Drug Design

2015 ◽  
Vol 16 (8) ◽  
pp. 701-717 ◽  
Author(s):  
Izabella Pena Neshich ◽  
Leticia Nishimura ◽  
Fabio de Moraes ◽  
Jose Salim ◽  
Fabian Villalta-Romero ◽  
...  
Keyword(s):  
Drug Design ◽  
Computational Biology ◽  
Ligand Binding ◽  
Binding Residues ◽  
Specific Ligand

Computational methods for calculation of protein-ligand binding affinities in structure-based drug design

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Zbigniew Dutkiewicz
Keyword(s):  
Drug Design ◽  
Ligand Binding ◽  
Binding Free Energy ◽  
Development Project ◽  
Quantum Mechanical ◽  
Prediction Methods ◽  
Binding Affinities ◽  
Structure Based Drug Design ◽  
Quantum Mechanical Description ◽  
Optimization Stage

AbstractDrug design is an expensive and time-consuming process. Any method that allows reducing the time the costs of the drug development project can have great practical value for the pharmaceutical industry. In structure-based drug design, affinity prediction methods are of great importance. The majority of methods used to predict binding free energy in protein-ligand complexes use molecular mechanics methods. However, many limitations of these methods in describing interactions exist. An attempt to go beyond these limits is the application of quantum-mechanical description for all or only part of the analyzed system. However, the extensive use of quantum mechanical (QM) approaches in drug discovery is still a demanding challenge. This chapter briefly reviews selected methods used to calculate protein-ligand binding affinity applied in virtual screening (VS), rescoring of docked poses, and lead optimization stage, including QM methods based on molecular simulations.

scholarly journals Extension of a de novo TIM barrel with a rationally designed secondary structure element

2021 ◽  
Vol 30 (5) ◽  
pp. 982-989
Author(s):  
Jonas Gregor Wiese ◽  
Sooruban Shanmugaratnam ◽  
Birte Höcker
Keyword(s):  
Secondary Structure ◽  
De Novo ◽  
Secondary Structure Element ◽  
Tim Barrel

Structural and Energetic Aspects of Protein-Ligand Binding in Drug Design

2000 ◽  
pp. 103-110 ◽  
Author(s):  
Gerhard Klebe ◽  
Markus Böhm ◽  
Frank Dullweber ◽  
Ulrich Grädler ◽  
Holger Gohlke ◽  
...  
Keyword(s):  
Drug Design ◽  
Ligand Binding

scholarly journals Alchemical Absolute Protein-Ligand Binding Free Energies for Drug Design

2021 ◽  
Author(s):  
Yuriy Khalak ◽  
Gary Tresdern ◽  
Matteo Aldeghi ◽  
Hannah Magdalena Baumann ◽  
David L. Mobley ◽  
...  
Keyword(s):  
Free Energy ◽  
Drug Discovery ◽  
Drug Design ◽  
Ligand Binding ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Free Energies ◽  
Energy Calculations ◽  
Binding Free Energy Calculations ◽  
Binding Free Energies

The recent advances in relative protein-ligand binding free energy calculations have shown the value of alchemical methods in drug discovery. Accurately assessing absolute binding free energies, although highly desired, remains...

scholarly journals Structure-Function of Neuronal Nicotinic Acetylcholine Receptor Inhibitors Derived From Natural Toxins

2020 ◽  
Vol 14 ◽  
Author(s):  
Thao N. T. Ho ◽  
Nikita Abraham ◽  
Richard J. Lewis
Keyword(s):  
Drug Design ◽  
Ligand Binding ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Molecular Mechanisms ◽  
Rational Drug Design ◽  
Comprehensive Overview ◽  
Nicotinic Acetylcholine ◽  
Structure Based Drug Design ◽  
Selective Ligand

Neuronal nicotinic acetylcholine receptors (nAChRs) are prototypical cation-selective, ligand-gated ion channels that mediate fast neurotransmission in the central and peripheral nervous systems. nAChRs are involved in a range of physiological and pathological functions and hence are important therapeutic targets. Their subunit homology and diverse pentameric assembly contribute to their challenging pharmacology and limit their drug development potential. Toxins produced by an extensive range of algae, plants and animals target nAChRs, with many proving pivotal in elucidating receptor pharmacology and biochemistry, as well as providing templates for structure-based drug design. The crystal structures of these toxins with diverse chemical profiles in complex with acetylcholine binding protein (AChBP), a soluble homolog of the extracellular ligand-binding domain of the nAChRs and more recently the extracellular domain of human α9 nAChRs, have been reported. These studies have shed light on the diverse molecular mechanisms of ligand-binding at neuronal nAChR subtypes and uncovered critical insights useful for rational drug design. This review provides a comprehensive overview and perspectives obtained from structure and function studies of diverse plant and animal toxins and their associated inhibitory mechanisms at neuronal nAChRs.

scholarly journals Relationship between Hot Spot Residues and Ligand Binding Hot Spots in Protein–Protein Interfaces

2012 ◽  
Vol 52 (8) ◽  
pp. 2236-2244 ◽  
Author(s):  
Brandon S. Zerbe ◽  
David R. Hall ◽  
Sandor Vajda ◽  
Adrian Whitty ◽  
Dima Kozakov
Keyword(s):  
Ligand Binding ◽  
Hot Spots ◽  
Hot Spot ◽  
Protein Interfaces
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