A new approach used in docking study for predicting the combination drug efficacy in EML4-ALK target of NSCLC.

Combination drug treatments are usually used in many diseases, including cancers and AIDS. This treatment strategy is known as one of the cornerstone in therapies, which potentially reduces drug toxicity and drug resistance and also enhances therapeutic efficacy. Before using a drug in treatment, several experimental studies are done in vivo and in vitro to ensure the drug's efficacy. In such experimental studies, the drug's efficacy is evaluated with the help of drug dose ratio. In the combination drug experimental studies, the efficacy of the drugs is quantified with the Combination Index (CI) value and then interpreted by various terminologies like synergy, additive, and antagonism. Several computational models have now been invented for the speedy identification of combination drug efficacy. Unfortunately, none of these models have predicted the atomic level interaction of the combination drug with the target protein. This type of intermolecular interaction can be identified with the help of docking software. In the proposed work, we try to identify the intermolecular interaction and efficacy of the combination drug Crzizotinib and Temozolomide in the target of EML4-ALK in NSCLC by in silico study. The result of the study was evaluated with drug properties and Complex Energy (CE) of the docked complex rather than using docking score and binding energy. From this study, we could understand that first, Crizotinib and then after the Temozolomide drug binded on the EML4-ALK protein complex, showed very least CE and also identified that the combination of Crizotinib and Temozolomide drug are more effective in NSCLC.Communicated by Ramaswamy H. Sarma.

Nature inspired optimization model for classification and severity prediction in COVID-19 clinical dataset.

The spread rate of COVID-19 is expected to be high in the wake of the virus's mutated strain found recently in a few countries. Fast diagnosis of the disease and knowing its severity are the two significant concerns of all physicians. Even though positive or negative diagnosis can be obtained through the RT-PCR test, an automatic model that predicts severity and the diagnosis will help medical practitioners to a great extend for affirming medication. Machine learning is an efficient tool that can process vast volume of data deposited in various formats, including clinical symptoms. In this work, we have developed machine learning models for analysing a clinical data set comprising 65000 records of patients, consisting of 26 features. An optimum set of features was derived from this data set by the proposed variant of artificial bee colony optimization algorithm. By making use of these features, a binary classifier is modelled with support vector machine for the screening of COVID-19 patients. Different models were tested for this purpose and the support vector machine has showcased the highest accuracy of 96%. Successively, severity prediction in COVID positive patients was also performed successfully by the logistic regression model. The model managed to predict three severity status viz mild, moderate, and severe. The confusion matrix and the precision-recall values (0.96 and 0.97) of the binary classifier indicate the classifier's efficiency in predicting positive cases correctly. The receiver operating curve generated for the severity predicting model shows the highest accuracy, 96.0% for class 1 and 85.0% for class 2 patients. Doctors can infer these results to finalize the type of treatment/care/facilities that need to be given to the patients from time to time.

Mining of structural motifs in proteins using artificial bee colony optimization framework for druggability.

In this work, we have developed an optimization framework for digging out common structural patterns inherent in DNA binding proteins. A novel variant of the artificial bee colony optimization algorithm is proposed to improve the exploitation process. Experiments on four benchmark objective functions for different dimensions proved the speedier convergence of the algorithm. Also, it has generated optimum features of Helix Turn Helix structural pattern based on the objective function defined with occurrence count on secondary structure. The proposed algorithm outperformed the compared methods in convergence speed and the quality of generated motif features. The motif locations obtained using the derived common pattern are compared with the results of two other motif detection tools. 92% of tested proteins have produced matching locations with the results of the compared methods. The performance of the approach was analyzed with various measures and observed higher sensitivity, specificity and area under the curve values. A novel strategy for druggability finding by docking studies, targeting the motif locations is also discussed.