Molecular Docking Study of (cid:11) -Cyclodextrin With Psoralen: MDA-MB-231 Cancer Cell

Psoralen is an important bioactive component, isolated from the leaves of Ficus carica (Fig). Psoralen is proved to inhibit breast cancer cell growth and in tumor bearing mice the function of osteoblasts and osteoclasts is regulated. It is difficult to treat Triple-Negative Breast Cancer, a sub type of breast cancer. On treating Fig leaf extract, it is found that the leaf extract inhibits the proliferation of MDA-MB-231, which is a TNBC cell line, but not MCF10A cells, which is normal breast epithelial cell line. To increase the stability, solubility, volatility, it is beneficial to encapsulate natural products with α-Cyclodextrin (α-CD). Cyclodextrin constituted by 6 glucose units are termed as α-Cyclodextrin. Compared to host molecule guest: host inclusion complexes exhibit improved chemical or biological properties. Main aim of the study is interaction of Psoralen with α-CD and MDA-MB-231 Cancer cell with α-CD: Psoralen inclusion complex by molecular docking studies. 3D structures of Psoralen, α-CD and MDA-MB-231 cancer cell are obtained and docking is carried out using PatchDock server. Model which is highly favorable will have a high score. Energetically favorable and most probable structures of α-CD: Psoralen and MDA-MB-231 cancer cell: α-CD Psoralen inclusion complex has a score of 1762 and 6230 respectively.


INTRODUCTION
Bioactive component, Psoralen is isolated from the leaves of icus carica ( ig) (Rashid et al., 2017). Breast cancer cell, MDA-MB-231, growth is found to be inhibited by Psoralen, without affecting normal breast cell, MCF10A (Zhang et al., 2018). Encapsulation of natural products leads to increase in sta-bility volatility etc., encapsulation has various applications including core material is protected from degradation, modi ication of physical characteristics, mask unwanted lavor or taste (Sebaaly et al., 2018). In cyclodextrin because of presence of pyranose ring, it has an internal hydrophobic cavity. External surface is hydrophilic due to presence of primary and secondary hydroxyl groups of glucose unit. CDs composed of 6 glucose units are called αcyclodextrin. CDs composed of 7 glucose units are called β-cyclodextrin and CDs composed of 8 glucose units are called γ-cyclodextrin (Carneiro et al., 2019). Inclusion complexes with α-CD improves solubility, physicochemical stability, shelf life of drugs, eliminate unpleasant taste and smell (Kfoury et al., 2016). Docking studies implies the best association of molecular interaction if their structures are given separately. Last 3 decades provides many docking algorithms like Z-Dock (Chen et al., 2002), GRAMM (Vakser et al., 1999), CAPRI (Inbar et al., 2005) and GOLD (Jones et al., 1997). The few web services are available for free nowadays (Comeau et al., 2004). For protein protein docking ef icient algorithm PatchDock has been developed. The best geometry based molecular docking algorithm is PatchDock, which gives good shape and molecular complementarity (Duhovny et al., 2002). The evaluation is done by scoring function, which involves atomic desolvation energy and clear geometric it (Zhang et al., 1997).
Root mean square deviation value is applied to minimize the redundant solutions. PatchDock is highly ef icient due to its run time less than 10 minutes.
The input is given in Protein Data Bank (PDB) ile format. For result noti ication user e-mail is mandatory. Some non-mandatory ields are also present (Schneidman- Duhovny et al., 2005).

Clustering RMSD
Proves that the distance between any two output solutions will be speci ied. The default value is 4s.

Complex Type
For different type of complexes, different parameters are optimized. The parameter set is optimized for small size molecules in case of protein-small ligand docking.

Molecular docking study of α-cyclodextrin with Psoralen and MDA-MB-231 cancer cells with α-CD: Psoralen complex
Using PatchDock server the molecular docking studies were carried out for Psoralen; α-CD; MDA-MB-231 cancer cells and determined the most favorable structure. ChemSpider database enable us to obtain the structure of α-CD (Roselet et al., 2017). The 3D structural data of Psoralen was obtained by translating its SDF format into PDB using PYMOL software. The 3D structural data of MDA-MB-231 cancer cell is obtained from Protein Data Bank using the search interface. PatchDock is used for docking the 3D structure of guest Psoralen into the host α-CD.

Docking of α-CD with Psoralen
The 3D structure of Psoralen is taken from Pub-Chem server and is shown in Figure 1. The 3D structure of α-CD is taken from ChemSpider and it is shown in Figure 2. Psoralen, the guest molecule is docked into α-CD, the host cavity by PatchDock server. The docked structure is viewed by PyMol software. On taking into account the score, interacting area, atomic contact energy and transformation value, various structures are obtained. These values are given in Table 1. Out of which 8 values are chosen. The model with high score value of 1762 is shown in Figure 3 and the lowest score is 756.   The docked structure is viewed by PyMol software. Considering the score value, interacting area, atomic contact energy and transformation value, various structures are obtained and the values are provided in Table 2. Out of which 10 values are chosen. A

CONCLUSIONS
The present study reveals the docking of α-CD with Psoralen and MDA-MB-231 cancer cell with α-CD: Psoralen complex. The study results are evaluated from score, interacting area, atomic contact energy values. The score value for α-CD: Psoralen complex is 1762, corresponding interaction area and atomic energies are 179.60Å and -105.41KJ/mol respectively. So this model is taken as the favored model. Similarly, the score value, interacting area and atomic energies of MDA-MB-231 cancer cell: α-CD Psoralen inclusion complex is 6230,707.40Å and -21.62KJ/mol respectively. Based on these values this model is considered as the preferred model.