Ab-initio density functional and docking studies of α-Santalol molecule derived from Santalum album: endorsing its reactive and inhibitory potential against Monkeypoxgp158 protein Anupam Sharma 1 , Anil Sharma 2 , Vandana Sharma 3 , Jatinder Kumar Sharma 3 , Om Prakash Singh 4 , Aanchal Sharma 5 , Seema Ramniwas 5 , Abhinav Sharma 6 , Varruchi Sharma 7 and Anil Kumar Sharma 8,* 1 MMIS, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala (Haryana) INDIA-133207. 2 DAV School, Barmana, Bilaspur, Himachal Pradesh, India. 3 Department of Physics, MMEC, Maharishi Markandeshwar (Deemed to be University), Mullana (Ambala) – 133207 (HARYANA), INDIA 4 Department of Physics, Paliwal (P.G.) College, Shikohabad – 205135 (U.P.) INDIA. 5 University Centre for Research and Development, University Institute of Biotechnology Chandigarh University, Gharuan, Mohali, India. 6 All India Institute of Medical Sciences (AIIMS), New Delhi, India. 7 Department of Biotechnology, Sri Guru Gobind Singh College Sector-26, Chandigarh (UT) India-160019. 8 Department of Biotechnology, M.M.E.C., Maharishi Markandeshwar (Deemed to be University), Mullana- Ambala (Haryana) India-133207. *Corresponding author: Professor and Head, Department of Biotechnology, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala-133207, Haryana, India. Abstract- α-Santalol (a sesquiterpene), an organic compound found in sandalwood was assessed for its reactive potential by computing bond length, Mullikan atomic charges, electrostatic potential surfaces, vibrational frequencies, polarizability, dipole moment and IR spectra with different basis sets implying Hartree Fock and Density functional theory (DFT) Redistribution of charges on α-Santalol was reported to be over a larger range along with the the Bond length values of C32-O39 reportedly higher than the corresponding values of O39-H40 suggestive of its reactivity mainly attributed to hydroxyl group (-OH) attached to C32.Molecular docking studies of α-Santalol with the Monkeypoxgp158 protein further indicate that the designed best probable ligand compound showed significant binding affinity i.e ΔG-8.4Kcal/mole across the binding cleft, suggestive of the therapeutic potential of α-Santalol against monkeypox. Quantum mechanical study of electronic structure, ground state properties and electrostatic potential surface study further supports the reactive sites present in α-Santalol. Keywords- Density functional studies; Electronic structure; Electrostatic potential; Mullikan atomic charges; α-Santalol; Molecular docking; Monkeypoxgp158 protein I. INTRODUCTION Santalum album L. is commonly known as East Indian sandalwood, Shrigandha, sandalwood and Chandana. This plant is the oldest, herbal plant which is well known for its unique and distinctive fragrance. The aromatic oil of Santalum album L.is used in a large variety of perfumes, food products, cosmetics, aromatherapy and pharmaceutical industries [1]. This plant is found to have therapeutic and pharmacological properties such as antioxidant, anticancer, anti-inflammatory, antiviral, antibacterial, antifungal, and cardio-protective properties[1-6]. The santalol comprises of 70–90% of sandalwood oil, which is obtained from the wood of a tree called Santalum album [1]. It is a tropical tree and its fragrant oil is used as a main component in perfumes.Tricyclic α -santalol have the Z-configuration at the side-chain double bond, however it exists in the E-configuration in small amounts in nature. Sandalwood oil is claimed to be very high in demand andrequirement; but this productbeingnatural is having very high cost. Moreover, its chemical synthesis is also not very cost-effective.The sandalwood oil has wide range of health benefits. Its antitumor and anticancer properties have been proved to cause cell death induction through apoptosis and cell cycle arrest in various cancer models[7,8].With α-Santalol administration in skin tissue models, a noticeable decrease in inflammatory markers has also been seen previously [7,8,9].α - Santalol, has also been shown to have chemo-preventive effects in a mouse model [9]. Moreover, studies have demonstrated 158 Journal of Xidian University https://doi.org/10.37896/jxu16.11/017 ISSN No:1001-2400 VOLUME 16, ISSUE 11, 2022 http://xadzkjdx.cn/