Target2DeNovoDrug: a novel programmatic tool for in silico-deep learning based de novo drug design for any target of interest

Abstract

The past decade has seen a surge in the range of application data science, machine learning, deep learning, and AI methods to drug discovery. The presented work involves an assemblage of a variety of AI methods for drug discovery along with the incorporation of in silico techniques to provide a holistic tool for automated drug discovery. When drug candidates are required to be identified for a particular drug target of interest, the user is required to provide the tool target signatures in the form of an amino acid sequence or its corresponding nucleotide sequence. The tool collects data registered on PubChem required to perform an automated QSAR and with the validated QSAR model, prediction and drug lead generation are carried out. This protocol we call Target2Drug. This is followed by a protocol we call Target2DeNovoDrug wherein novel molecules with likely activity against the target are generated de novo using a generative LSTM model. It is often required in drug discovery that the generated molecules possess certain properties like drug-likeness, and therefore to optimize the generated de novo molecules toward the required drug-like property we use a deep learning model called DeepFMPO, and this protocol we call Target2DeNovoDrugPropMax. This is followed by the fast automated AutoDock-Vina based in silico modeling and profiling of the interaction of optimized drug leads and the drug target. This is followed by an automated execution of the Molecular Dynamics protocol that is also carried out for the complex identified with the best protein-ligand interaction from the AutoDock-Vina based virtual screening. The results are stored in the working folder of the user. The code is maintained, supported, and provide for use in the following GitHub repository

Analysis of genetic profiling, pathomics signature, and prognostic features of primary lymphoepithelioma‐like carcinoma of the renal pelvis

“…Cluster analysis was performed on the tumor cells to determine the clonal structure of the tumor samples. Based on the detection of somatic mutations in tumor samples, the detected mutation sites were compared with the NovoDR drug‐resistant gene databases [ 26 ] to screen for possible cancer drug‐resistant mutations.…”

“…Cluster analysis was performed on the tumor cells to determine the clonal structure of the tumor samples. Based on the detection of somatic mutations in tumor samples, the detected mutation sites were compared with the NovoDR drug-resistant gene databases [26] to screen for possible cancer drug-resistant mutations. The clinicopathologic features and survival data of UUT-UC and LELC of upper urinary tract patients were obtained from the SEER database, which contains official clinicopathologic and follow-up reports from 18 population-based tumor registries that mainly embody the U.S. patient population [27].…”

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