A Computer Aided Drug Designing Approach to Target the KRAS protein with Ligand DON to treat Lung Cancer

Author Name: *Brwa Abdulrahman Abubaker
Author Email: brwa.pshdary@gmail.com


Development of Drugs towards ailments was one of the oldest techniques followed since ages. Though the technique was proved to be effective one of the major drawbacks is the time involved in development of a drug using traditional Methods. The Computer Aided Drug Designing or the Rational Drug designing is one of the best solutions for the problems faced by the traditional method. The current work aims to develop a potential drug molecule to target the K RAS protein, vital in the onset of cancer. This aim is achieved by employing the CADD approach. The sequence of the K RAS was retrieved from NCBI data base and the sequence analysis was performed using various bioinformatics tools to annotate the protein. The Functional study of the protein was also performed using SMART, ProtParam, Fingerprint Scan and CDD analysis. The Structural study was performed using ExPASy’s tools. The secondary confirmations in the protein were studied using SOPMA and the tertiary structure’s PDB Id was obtained using Phyre. The 3D structure of the protein was obtained from RCSB Protein Data Bank. The structure was visualized using RASMOL software. The Lead chemicals were collected from PubChem Data base. The screening of the chemicals was performed for various parameters like Drug Likeliness and Ambiguity. The final list of chemicals was processed for docking with the K RAS receptor using HEX 8.00 Software. Based on the docking result, the best drug selected for the KRAS receptor was DON with the CID 5359375.


CADD, SMART, DON, K Ras, Docking


KRAS, also called Kras, K-RAS, or KRAS2, is a gene that is important in cell growth and tumor development. The KRAS gene is mutated in about 25% of NSCLC cases. Patients are usually tested for the KRAS and EGFR biomarkers at the same time, because the presence of both (Complete statement), Approximately 15–25% of patients with lung adenocarcinoma have tumor associated KRAS mutations. KRASmutations are uncommon in lung squamous cell carcinoma. Several approaches have been implemented in relation to the cancer therapy. The use of bioinformatics in cancer therapy is emerging very drastically and has gained full attention. In Computer aided drug desigining or rational drug design, biologically active compounds are specifically designed or chosen to work with a particular drug target. This method often involves the use of molecular design software, which researchers use to create three-dimensional models of drugs and their biological targets [3]. Drug designing requires the Chemical leads to be screened which are intern obtain deom various databases and sources. One such database is the Pubchem. This is the product of NCB. This contains chemical molecules along with the annotations about their bioactivity, Molecular Properties, Analogues etc. All the chemical from this database are also linked tp their uses and application till the date of their updation. Each chemical in in Pubchem has been assigned a CID No which represents the structure. Docking is a phenomena of a ligand binding to its receptor. Protein-protein interactions play a central role in various aspects of the structural and functional organization of the cell, signal transduction, and gene regulation. In Drug designing a dock in performed between a chemical lead and the protein receptor to test the binding feasibility and analyze the energy of the pair. Based on the docking results the best ligand can be selected, however the function of the ligand is a separate issue to be dealt with.


The current work aimed to study the KRAS protein ,one of the major causes of Lung Cancer. KRAS protein was retrieved from NCBI database. The sequence, Functional and Structural analysis was performed using various insilio tools and data bases. The 3D structure of the protein was downloaded from RCSB Protein databank whose PDB id was obtained from Phyre tool. The PDB id selected for the KRAS protein was 1CTQ having 95% similarity with the sequence. The structure was visualized using RASMOL software. The chemicals were obtained from the Pubchem data base. All the chemicals were screened based on the functionality. The selected chemicals were further screened for Drug likeliness based on Lipinki rule. All the final selected leads were screened for Ambiguity using Dundee Prodrg Server. The final chemical selected was DON with the CID no CID 5359375Docking was performed between DON and KRAS in the software Hex. The docking energy was calculated to be -182.84 which an indication of a good docking couple. The current study concludes that DON can be used for targeting the KRAS protein involved in Lung cancer.

46 total views, 1 views today

Download File

About the author: dev