Protein-protein Interactions: Network Analysis and Applications in Drug Discovery

Bultinck, Jennyfer; Lievens, Sam; Tavernier, Jan

doi:10.2174/138161212802651562

Cited by 28 publications

(12 citation statements)

References 123 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Targeting these non-hub nodes (with the exception of infectious diseases and cancer) is crucial to avoid unwanted side-effects. As opposed to targets of withdrawn drugs having a too large network influence, drug target proteins perturb the interactome in a controlled manner (Hase et al, 2009; Zhu et al, 2009; Butlinck et al, 2012; Yu & Huang, 2012). …”

Section: The Use Of Molecular Network In Drug Designmentioning

confidence: 99%

Structure and dynamics of molecular networks: A novel paradigm of drug discovery

Csermely

Korcsmáros

Kiss

et al. 2013

Pharmacology & Therapeutics

809

661

View full text Add to dashboard Cite

Despite considerable progress in genome- and proteome-based high-throughput screening methods and in rational drug design, the increase in approved drugs in the past decade did not match the increase of drug development costs. Network description and analysis not only gives a systems-level understanding of drug action and disease complexity, but can also help to improve the efficiency of drug design. We give a comprehensive assessment of the analytical tools of network topology and dynamics. The state-of-the-art use of chemical similarity, protein structure, protein-protein interaction, signaling, genetic interaction and metabolic networks in the discovery of drug targets is summarized. We propose that network targeting follows two basic strategies. The “central hit strategy” selectively targets central node/edges of the flexible networks of infectious agents or cancer cells to kill them. The “network influence strategy” works against other diseases, where an efficient reconfiguration of rigid networks needs to be achieved. It is shown how network techniques can help in the identification of single-target, edgetic, multi-target and allo-network drug target candidates. We review the recent boom in network methods helping hit identification, lead selection optimizing drug efficacy, as well as minimizing side-effects and drug toxicity. Successful network-based drug development strategies are shown through the examples of infections, cancer, metabolic diseases, neurodegenerative diseases and aging. Summarizing >1200 references we suggest an optimized protocol of network-aided drug development, and provide a list of systems-level hallmarks of drug quality. Finally, we highlight network-related drug development trends helping to achieve these hallmarks by a cohesive, global approach.

show abstract

Section: The Use Of Molecular Network In Drug Designmentioning

confidence: 99%

Structure and dynamics of molecular networks: A novel paradigm of drug discovery

Csermely

Korcsmáros

Kiss

et al. 2013

Pharmacology & Therapeutics

809

661

View full text Add to dashboard Cite

show abstract

“…Network based drug discovery has become a recurrent theme for natural compounds too; characterization of the drug regulated genes and targets have been assisted greatly by computational techniques [78–80]. Rational drug designing from natural sources have made drug costs and required resources to go down significantly over the years [81–83]. Hence this study holds great implications for drug designing from natural products [84–86].…”

Section: Discussionmentioning

confidence: 99%

Docking studies and network analyses reveal capacity of compounds from Kandelia rheedii to strengthen cellular immunity by interacting with host proteins during tuberculosis infection

Zaman

2012

Bioinformation

View full text Add to dashboard Cite

Kandelia rheedii (locally known as Guria or Rasunia), widely found and used in Indian subcontinent, is a well-known herbal cure to tuberculosis. However, neither the mechanism nor the active components of the plant extract responsible for mediating this action has yet been confirmed. Here in this study, molecular interactions of three compounds (emodin, fusaric acid and skyrin) from the plant extract with the host protein targets (casein kinase (CSNK), estrogen receptor (ERBB), dopamine β-hydroxylase (DBH) and glucagon receptor (Gcgr)) has been found. These protein targets are known to be responsible for strengthening cellular immunity against Mycobacteria tuberculosis. The specific interactions of these three compounds with the respective protein targets have been discussed here. The insights from study should further help us designing molecular medicines against tuberculosis.

show abstract

“…Therefore, in the past few years, with the emergence of high-throughput technologies for omics data, like yeast 2 hybrid protein interactions, research of protein-protein interactions (PPI) has been occurring with high frequency. Bultinck et al [10] concluded that a growing number of functional PPI modulators are being reported and clinically evaluated. PPI provides us with more information for understanding the relationship between drug targets and other proteins in a systematic point of view.…”

Section: Introductionmentioning

confidence: 99%

Drug Target Protein-Protein Interaction Networks: A Systematic Perspective

Feng

Wang

2017

BioMed Research International

View full text Add to dashboard Cite

The identification and validation of drug targets are crucial in biomedical research and many studies have been conducted on analyzing drug target features for getting a better understanding on principles of their mechanisms. But most of them are based on either strong biological hypotheses or the chemical and physical properties of those targets separately. In this paper, we investigated three main ways to understand the functional biomolecules based on the topological features of drug targets. There are no significant differences between targets and common proteins in the protein-protein interactions network, indicating the drug targets are neither hub proteins which are dominant nor the bridge proteins. According to some special topological structures of the drug targets, there are significant differences between known targets and other proteins. Furthermore, the drug targets mainly belong to three typical communities based on their modularity. These topological features are helpful to understand how the drug targets work in the PPI network. Particularly, it is an alternative way to predict potential targets or extract nontargets to test a new drug target efficiently and economically. By this way, a drug target's homologue set containing 102 potential target proteins is predicted in the paper.

show abstract

Protein-protein Interactions: Network Analysis and Applications in Drug Discovery

Cited by 28 publications

References 123 publications

Structure and dynamics of molecular networks: A novel paradigm of drug discovery

Structure and dynamics of molecular networks: A novel paradigm of drug discovery

Docking studies and network analyses reveal capacity of compounds from Kandelia rheedii to strengthen cellular immunity by interacting with host proteins during tuberculosis infection

Drug Target Protein-Protein Interaction Networks: A Systematic Perspective

Contact Info

Product

Resources

About