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Molecular docking analysis of KRAS inhibitors for cancer management



Israa J. Hakeem1, Fatmah Hazza Alsharif2, Majidah Aljadani3, Ibrahim Fahad Alabbas4, Mohammed Saud Faqihi5, Ahmed Hamdan Aloufi6, Wael Abdullah Almutairi7, Asif Hussain Akber8 & Qamre Alam9,*



1Department of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi Arabia; 2Department of Medical Surgical Nursing Oncology and Palliative Care Nursing, Faculty of Nursing, King Abdulaziz University, Jeddah, Saudi Arabia; 3Department of Chemistry, College of Sciences & Arts, King Abdulaziz University, Rabigh, Saudi Arabia; 4Central Military Laboratory and Blood Bank Department - Virology Division, Prince Sultan Military Medical City, Riyadh 12233, Saudi Arabia; 5Central Military Laboratory and Blood Bank Department Microbiology Division, Prince Sultan Military Medical City, Riyadh 12233, Saudi Arabia; 6Department of Pathology and Laboratory Medicine, Imam Abdulrahman bin Faisal Hospital Ministry of National Guard Health Affairs, P.O. Box 34232 Dhahran, Saudi Arabia; 7Department of Respiratory Services, Ministry of National Guard Hospital and Health Affairs (MNGHA) P.O. box 22490, kingdom of Saudi Arabia; 8Central Military Laboratory and Blood Bank Department - Virology Division, Prince Sultan Military Medical City, Riyadh 12233, Saudi Arabia; 9Molecular Genomics and Precision Medicine Department, ExpressMed laboratories, Block, 359, Zinj, Kingdom of Bahrain; *Corresponding author



Israa J. Hakeem - Email: ijhakeem@uj.edu.sa
Fatmah Hazza Alsharif - Email: Falsharif@kau.edu.sa
Majidah Aljadani - Email: maaljadani@kau.edu.sa
Ibrahim Fahad Alabbas - Email: ialabbas@psmmc.med.sa
Mohammed Saud Faqihi - Email: msfaqihi@psmmc.med.sa
Ahmed Hamdan Aloufi - Email: aloufiah@ngha.med.sa
Wael Abdullah Almutairi - Email: Almutairiwa3@ngha.med.sa
Asif Hussain Akber Email: asif20000@gmail.com
Qamre Alam - Email: alamqa2022@gmail.com, qamrealam@expressmedlabs.com

Article Type

Research Article



Received April 1, 2023; Revised April 30, 2023; Accepted April 30, 2023, Published April 30, 2023



The majority of human tumors are characterized by abnormal signaling caused by oncogenic RAS proteins. KRAS is a member of the RAS family and is currently one of the most thoroughly researched targets for cancer treatment due to its prevalence in a variety of deadly malignancies. Targeting the KRAS protein, which plays a crucial role in regulating cell growth, differentiation, and apoptosis, shows great potential as a strategy for fighting cancer. Herein, in silico screening of 530 natural compounds against KRAS protein was performed. The top-scoring hits, namely ZINC32502206, ZINC98363763, ZINC85645815, and ZINC98364259 displayed a robust affinity towards KRAS as evidenced by their respective binding affinity values of -10.50, -10.01, -9.80, and -9.70 kcal/mol, respectively which were notably higher than that of the control compound AMG 510 (-9.10 kcal/mol). Through virtual screening and visual inspection, it was observed that these hits effectively interacted with the essential residues located within the active site of KRAS. Based on the findings of this study, it can be inferred that these compounds may have the potential to be employed in the treatment of cancer by targeting KRAS.



Cancer, KRAS, natural compounds, inhibitors, virtual screening



Hakeem et al. Bioinformation 19(4): 411-416 (2023)


Edited by

P Kangueane






Biomedical Informatics



This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.