Protein-Protein Interactions: Principles, Techniques, and their Potential Role in New Drug Development

Abstract

A vast network of genes is inter-linked through protein-protein interactions and is critical component of almost every biological process under physiological conditions. Any disruption of the biologically essential network leads to pathological conditions resulting into related diseases. Therefore, proper understanding of biological functions warrants a comprehensive knowledge of protein-protein interactions and the molecular mechanisms that govern such processes. The importance of protein-protein interaction process is highlighted by the fact that a number of powerful techniques/methods have been developed to understand how such interactions take place under various physiological and pathological conditions. Many of the key protein-protein interactions are known to participate in disease-associated signaling pathways, and represent novel targets for therapeutic intervention. Thus, controlling protein-protein interactions offers a rich dividend for the discovery of new drug targets. Availability of various tools to study and the knowledge of human genome have put us in a unique position to understand highly complex biological network, and the mechanisms involved therein. In this review article, we have summarized protein-protein interaction networks, techniques/methods of their binding/kinetic parameters, and the role of these interactions in the development of potential tools for drug designing.

Reactive oxygen species and energy machinery: an integrated dynamic model

“…Results of molecular dynamics simulation, carried out to study protein-ligand interaction (Verma, Singh & Mishra, 2015), can be incorporated in the script to study the overall interaction with the system. Another interesting aspect could be integrating simulation scripts with protein-protein interaction networks, their kinetic parameters, and expanding the studies for development of potential tools for drug designing (Khan, Ahmad, Ahmad, Flynn & Kumar, 2011).…”

A novel index of protein-protein interface propensity improves interface residue recognition

“…A detailed characterization of protein-protein interactions may provide crucial information about the function of protein complexes which would be helpful in medicine and drug researches [4–6]. In order to elucidate the mechanisms of protein-protein interactions, a number of biophysical techniques [7, 8] including X-ray crystallography, various spectroscopic techniques, cross-linking methods, mutation studies and so on, have been employed to investigate protein-protein interface properties. Meanwhile, a lot of efforts have been made to find the critical factors determining the specificity and affinity of protein–protein interfaces [3, 9–11].…”

Host–rabies virus protein–protein interactions as druggable antiviral targets

“…MPCs represent the core of the protein-protein interaction (PPI) networks responsible for a multitude of biological functions (23,24). Effective therapeutic modulation of MPC PPIs would be powerful (25,26), but a history of unsuccessful attempts has led to the widespread opinion that such targets are not druggable (19). We hypothesize that these setbacks can be attributed to the limitations imposed by both traditional drugs and traditional approaches to drug discovery and that a different approach might be successful.…”