Antimalarial Drug Discovery: In Silico Structural Biology and Rational Drug Design

AbstractThe reductionist approach is prevalent in biomedical science. However, increasing evidence now shows that biological systems cannot be simply considered as the sum of its parts. With experimental, technological, and computational advances, we can now do more than view parts in isolation, thus we propose that an increasing holistic view (where a protein is investigated as much as a whole as possible) is now timely. To further advocate this, we review and discuss several studies and applications involving allostery, where distant protein regions can cross-talk to influence functionality. Therefore, we believe that an increasing big picture approach holds great promise, particularly in the areas of antibody engineering and drug discovery in rational drug design.

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Rational Drug Design Using Integrative Structural Biology

Methods in Molecular Biology - Rational Drug Design ◽

10.1007/978-1-4939-8630-9_6 ◽

2018 ◽

pp. 89-111 ◽

Cited By ~ 1

Author(s):

Magda S. Chegkazi ◽

Michael Mamais ◽

Anastasia I. Sotiropoulou ◽

Evangelia D. Chrysina

Keyword(s):

Drug Design ◽

Structural Biology ◽

Rational Drug Design ◽

Rational Drug ◽

Integrative Structural Biology

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Faculty Opinions recommendation of In silico ADME/T modelling for rational drug design.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725769511.793523380 ◽

2016 ◽

Author(s):

Stevan Djuric

Keyword(s):

Drug Design ◽

In Silico ◽

Rational Drug Design ◽

Rational Drug

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Mechanisms of Action for Small Molecules Revealed by Structural Biology in Drug Discovery

International Journal of Molecular Sciences ◽

10.3390/ijms21155262 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5262 ◽

Cited By ~ 1

Author(s):

Qingxin Li ◽

CongBao Kang

Keyword(s):

Drug Discovery ◽

Small Molecules ◽

Structural Biology ◽

Small Molecule ◽

Molecular Interactions ◽

Mechanisms Of Action ◽

Rational Drug Design ◽

Binding Modes ◽

Small Molecule Drugs ◽

Rational Drug

Small-molecule drugs are organic compounds affecting molecular pathways by targeting important proteins. These compounds have a low molecular weight, making them penetrate cells easily. Small-molecule drugs can be developed from leads derived from rational drug design or isolated from natural resources. A target-based drug discovery project usually includes target identification, target validation, hit identification, hit to lead and lead optimization. Understanding molecular interactions between small molecules and their targets is critical in drug discovery. Although many biophysical and biochemical methods are able to elucidate molecular interactions of small molecules with their targets, structural biology is the most powerful tool to determine the mechanisms of action for both targets and the developed compounds. Herein, we reviewed the application of structural biology to investigate binding modes of orthosteric and allosteric inhibitors. It is exemplified that structural biology provides a clear view of the binding modes of protease inhibitors and phosphatase inhibitors. We also demonstrate that structural biology provides insights into the function of a target and identifies a druggable site for rational drug design.

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