The cancer cell prolonged and continues proliferation is a major cause of tumorigenesis. In general, Insulin like growth factor receptor (IGF-1R) and Insulin receptor (IR-A) protein are responsible for such cell proliferations. However, with respect to cancers, the specific over-expression of these receptors along with the elevated levels of their agonist, i.e. insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2) have shown to be the integral part of cancer cell’s proliferation. The understanding of the dual targeting of (IR) and (IGF-1R) through Artificial Intelligence in tumorigenesis is now considered to be a possible aspect to achieve the desired results. In this research we signify that according to data based on artificial intelligence, the tyrosine kinase domain of these two receptors can accommodates number of small molecules inhibitors to block the ongoing signaling cascade for cell proliferation. It is indeed found to be of paramount importance to develop such candidates as clinical solutions to block the activity of tyrosine kinase domain of IR and IGF-1R. Therefore, this study aims to use artificial intelligence for understanding the key molecular interactions responsible for activation and inhibition of the proliferation signal via tyrosine kinase domain. Further, we optimized docking protocol on crystal structures of such system from protein databank. Our study revealed that H-bond donor and hydrophobic pocket play a key role in the initiation of the signal cascade for cell proliferation. The simulations ran produced an acceptable solution based on the statistical measures of Mathew’s correlation factor and delineated two H- bonds distances between 12-22. Our study also concluded that how a docking protocol can be optimized to accommodate the non-congeneric series small molecules. We successfully ran the simulation to conclude that LYS 1030, GLU 1077, MET 1079 and ASP 1083 amino acids positions play an important role in binding of small molecules to inhibit cancer cell proliferation. This research bridges the gap between in-silico and in-vitro experimentations and paves a way to reproduce the results experimentally.

The cell cycle is a conserved process comprising of an organized series of interdependent and cross regulatory events that lead to controlled cell growth and proliferation. Genomic and volume regulatory processes are of special interest as they decide the fate of cell cycle. Signaling cascades including MAPK, PI3K, Sonic Hedgehog, Wnt and NOTCH signaling pathways are few well known conventional players contributing in controlling the cell cycle progression through different phases by expressing certain proteins. Moreover, the unconventional volume regulatory players exert influence by regulating membrane potential that is determined by ions influx or efflux across the plasma membrane via ion channels, controlling water movement and ultimately contributing to volume increase in growth phases of the cell cycle. Both of these players are interlinked, therefore, in order to establish a better understanding of the interdependence of these players, principles of machine learning were applied on data obtained on cell cycle. The data was processed by using neural networks and it shows that a significant understanding of conventional regulators is available in the literature and it has been under the limelight as well. However, when it comes to unconventional volume regulatory players, a limited understanding is available. Moreover, the precise role of each component and its interdependence with other is not yet fully understood. Due to which, they are not clearly evaluated for their potential role as cell cycle control elements for therapeutic purposes. Therefore, this study aims to summarize the data on cell cycle that is obtained through machine learning and to discuss the advances in cell cycle modelling mechanisms and designs that are based on different mathematical algorithms. Thus, this review will provide a basis to clearly understand and interlink the discoveries on cell cycle so that a comprehensive cell cycle model could be built which, if manipulated can be used for therapeutic purposes by identifying the least explored regulatory control elements.