Systems biology seeks to understand phenotypes as a consequence of a dynamic and spatiotemporally orchestrated involvement of genes, RNA and and/or proteins within cells. With the advent of next generation high throughput technologies, specialized cellular functions and physiological milestones are now widely accepted to be an outcome of concerted molecular events that occur within the genome, transcriptome and ultimately the proteome.
In recent years systems approaches have been proposed to unravel the pharmacological complexities surrounding drug-protein interactions including the rewiring of cellular protein networks and signaling mechanisms in response to drugs, and other compound screening paradigms. Integrating system-wide approaches to pharmacology, fundamentally conceptualizes the principle of Systems Pharmacology where the primary objective is to understand the global impact chemical or biological agents exert on cells at a molecular level to eventually affect the physiological state.
At the molecular level, aberrant protein expression and/or activity is biologically undesirable and can lead to disease. Proteins, therefore, represent prime targets for therapy. However, target protein discovery requires essential biochemical knowledge including but not limited to information on the protein-binding specificity responsible for mediating crucial protein-protein interactions (PPIs) and substrate specificity in the case of kinases. Next, the target protein’s cellular signaling profile assumes importance in implicating its role in disease. Finally, mechanisms to screen candidate drugs or other therapeutic agents against target protein(s) must be designed while recognizing the inevitable potential for off-target effects. In certain cases, identities of protein(s) and the extent of their affinities to uncharacterized drugs such as naturally derived bioactive compounds also pose a challenge and need to be determined for making informed progress towards precision medicine.
A rational approach to medicine calls for holistic efforts to:
(i) understand how molecular networks are altered on a global scale,
(ii) rationalize robust targets and,
(iii) design appropriate screening methodologies to capture on and off-target activity of candidate compounds.
This special edition focuses on Systems Pharmacology and seeks to explore innovative and cutting-edge tools and technologies in systems biology with either direct fundamental or indirect applications in pharmacology. We invite original research articles, reviews or opinion on concepts and themes that include but are not limited to:
1. Proximity labeling to study drug-protein and protein-protein interactions: Biotinylation and/or Ubiquitination-based targeting (e.g. PROTAC)
2. Thermal shift assays to elucidate protein target(s), off-target/indirect targets of uncharacterized compounds (e.g. CETSA)
3. Kinase-substrate specificity
4. Small-molecule compound screening
5. Precision proteomics to survey drug response in vitro or in vivo
In silico studies are not acceptable unless these substantially incorporate or are supported by experimental evidence.
Systems biology seeks to understand phenotypes as a consequence of a dynamic and spatiotemporally orchestrated involvement of genes, RNA and and/or proteins within cells. With the advent of next generation high throughput technologies, specialized cellular functions and physiological milestones are now widely accepted to be an outcome of concerted molecular events that occur within the genome, transcriptome and ultimately the proteome.
In recent years systems approaches have been proposed to unravel the pharmacological complexities surrounding drug-protein interactions including the rewiring of cellular protein networks and signaling mechanisms in response to drugs, and other compound screening paradigms. Integrating system-wide approaches to pharmacology, fundamentally conceptualizes the principle of Systems Pharmacology where the primary objective is to understand the global impact chemical or biological agents exert on cells at a molecular level to eventually affect the physiological state.
At the molecular level, aberrant protein expression and/or activity is biologically undesirable and can lead to disease. Proteins, therefore, represent prime targets for therapy. However, target protein discovery requires essential biochemical knowledge including but not limited to information on the protein-binding specificity responsible for mediating crucial protein-protein interactions (PPIs) and substrate specificity in the case of kinases. Next, the target protein’s cellular signaling profile assumes importance in implicating its role in disease. Finally, mechanisms to screen candidate drugs or other therapeutic agents against target protein(s) must be designed while recognizing the inevitable potential for off-target effects. In certain cases, identities of protein(s) and the extent of their affinities to uncharacterized drugs such as naturally derived bioactive compounds also pose a challenge and need to be determined for making informed progress towards precision medicine.
A rational approach to medicine calls for holistic efforts to:
(i) understand how molecular networks are altered on a global scale,
(ii) rationalize robust targets and,
(iii) design appropriate screening methodologies to capture on and off-target activity of candidate compounds.
This special edition focuses on Systems Pharmacology and seeks to explore innovative and cutting-edge tools and technologies in systems biology with either direct fundamental or indirect applications in pharmacology. We invite original research articles, reviews or opinion on concepts and themes that include but are not limited to:
1. Proximity labeling to study drug-protein and protein-protein interactions: Biotinylation and/or Ubiquitination-based targeting (e.g. PROTAC)
2. Thermal shift assays to elucidate protein target(s), off-target/indirect targets of uncharacterized compounds (e.g. CETSA)
3. Kinase-substrate specificity
4. Small-molecule compound screening
5. Precision proteomics to survey drug response in vitro or in vivo
In silico studies are not acceptable unless these substantially incorporate or are supported by experimental evidence.
