The Open Biochemistry Journal

ISSN: 1874-091X ― Volume 14, 2020

Screening Outside the Catalytic Site: Inhibition of Macromolecular Interactions Through Structure-Based Virtual Ligand Screening Experiments

Olivier Sperandio1, Maria A Miteva1, Kenneth Segers2, Gerry A. F Nicolaes2, Bruno O Villoutreix*, 1
1 Inserm U648, University of Paris 5, 45 rue des Sts Peres, 75006 Paris, France
2 Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands


During these last 15 years, drug discovery strategies have essentially focused on identifying small molecules able to inhibit catalytic sites. However, other mechanisms could be targeted. Protein-protein interactions play crucial roles in a number of biological processes, and, as such, their disruption or stabilization is becoming an area of intense activity. Along the same line, inhibition of protein-membrane could be of major importance in several disease indications. Despite the many challenges associated with the development of such classes of interaction modulators, there has been considerable success in the recent years. Importantly, through the existence of protein hot-spots and the presence of druggable pockets at the macromolecular interfaces or in their vicinities, it has been possible to find small molecule effectors using a variety of screening techniques, including combined virtual ligand-in vitro screening strategy. Indeed such in silico-in vitro protocols emerge as the method of choice to facilitate our quest of novel drug-like compounds or of mechanistic probes aiming at facilitating the understanding of molecular reactions involved in the Health and Disease process. In this review, we comment recent successes of combined in silico-in vitro screening methods applied to modulating macromolecular interactions with a special emphasis on protein-membrane interactions.

Keywords: Virtual screening, structure-based drug design, drug discovery, protein-protein interaction, protein-membrane interaction.

Article Information

Identifiers and Pagination:

Year: 2008
Volume: 2
First Page: 29
Last Page: 37
Publisher Id: TOBIOCJ-2-29
DOI: 10.2174/1874091X00802010029

Article History:

Received Date: 20/1/2008
Revision Received Date: 8/2/2008
Acceptance Date: 23/2/2008
Electronic publication date: 10/3/2008
Collection year: 2008

2008 Bentham Science Publishers Ltd

* Address correspondence to this author at the Inserm U648, University of Paris 5, 45 rue des Sts Peres, 75006 Paris, France; E-mail:

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