Hydration in drug design. 1. Multiple hydrogen-bonding features of water molecules in mediating protein-ligand interactions

1995 ◽  
Vol 9 (6) ◽  
pp. 500-512 ◽  
Author(s):  
C. S. Poornima ◽  
P. M. Dean
Keyword(s):  
Hydrogen Bonding ◽  
Drug Design ◽  
Water Molecules ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Multiple Hydrogen Bonding

scholarly journals Structure- and ligand-based drug design approaches for neglected tropical diseases

2012 ◽  
Vol 84 (9) ◽  
pp. 1857-1866 ◽  
Author(s):  
Rafael V. C. Guido ◽  
Glaucius Oliva ◽  
Adriano D. Andricopulo
Keyword(s):  
Drug Design ◽  
Neglected Tropical Diseases ◽  
Poor People ◽  
Tropical Diseases ◽  
Protein Ligand Interactions ◽  
New Chemical Entities ◽  
Ligand Interactions ◽  
Complementary Nature ◽  
Further Development ◽  
D Investment

Drug discovery has moved toward more rational strategies based on our increasing understanding of the fundamental principles of protein–ligand interactions. Structure- (SBDD) and ligand-based drug design (LBDD) approaches bring together the most powerful concepts in modern chemistry and biology, linking medicinal chemistry with structural biology. The definition and assessment of both chemical and biological space have revitalized the importance of exploring the intrinsic complementary nature of experimental and computational methods in drug design. Major challenges in this field include the identification of promising hits and the development of high-quality leads for further development into clinical candidates. It becomes particularly important in the case of neglected tropical diseases (NTDs) that affect disproportionately poor people living in rural and remote regions worldwide, and for which there is an insufficient number of new chemical entities being evaluated owing to the lack of innovation and R&D investment by the pharmaceutical industry. This perspective paper outlines the utility and applications of SBDD and LBDD approaches for the identification and design of new small-molecule agents for NTDs.

Improving protein–ligand binding prediction by considering the bridging water molecules in Autodock

2019 ◽  
Vol 18 (05) ◽  
pp. 1950027 ◽  
Author(s):  
Qiangna Lu ◽  
Lian-Wen Qi ◽  
Jinfeng Liu
Keyword(s):  
Ligand Binding ◽  
Considerable Improvement ◽  
Ligand Docking ◽  
Water Molecules ◽  
Binding Modes ◽  
Binding Prediction ◽  
Docking Simulations ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Docking Program

Water plays a significant role in determining the protein–ligand binding modes, especially when water molecules are involved in mediating protein–ligand interactions, and these important water molecules are receiving more and more attention in recent years. Considering the effects of water molecules has gradually become a routine process for accurate description of the protein–ligand interactions. As a free docking program, Autodock has been most widely used in predicting the protein–ligand binding modes. However, whether the inclusion of water molecules in Autodock would improve its docking performance has not been systematically investigated. Here, we incorporate important bridging water molecules into Autodock program, and systematically investigate the effectiveness of these water molecules in protein–ligand docking. This approach was evaluated using 18 structurally diverse protein–ligand complexes, in which several water molecules bridge the protein–ligand interactions. Different treatment of water molecules were tested by using the fixed and rotatable water molecules, and a considerable improvement in successful docking simulations was found when including these water molecules. This study illustrates the necessity of inclusion of water molecules in Autodock docking, and emphasizes the importance of a proper treatment of water molecules in protein–ligand binding predictions.

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