Department of Physics, Manonmaniam Sundaranar University, Tirunelveli, India.
Department of Animal Nutrition, Veterinary College and Research Institute, Tamil Nadu Veterinary and Animal Sciences University, Tirunelveli, India.
J Biomol Struct Dyn. 2022 Jul;40(11):5036-5052. doi: 10.1080/07391102.2020.1866075. Epub 2020 Dec 29.
Main focus of study is to understand potency of halogen (X = Br) atom that exists in tetrabromobenzotriazole (TBB) derivatives of crystal CK2 ligand along with hinge region amino acids (VAL45, PHE113, GLU114, VAL116, ASN118) through interaction energy analysis. In turn to attain profound insight on nature of stabilization of core CK2 ligands: 1ZOE-L1, 1ZOG-L2, 1ZOH-L3, 2OXX-L4, 2OXY-L5, 3KXG-L6, 3KXH-L7 -L7 and 3KXM-L8, having four bromine atoms, we attempted to mutate all bromine (X = Br) atoms by various functional groups (X = Cl, F, CF, CH, NH, OH, H) and binding strength along with amino acids was calculated. Most stable ligands exist in mutated NH functional groups: 1ZOG-L2, 1ZOH-L3, 2OXX-L4, 3KXM-L8 having interaction energy as -5.21, -14.87, -6.69 and -11.72 kcal/mol respectively, revealing strong binding strength. Second most stable mutated Cl functional group ligands also play a major role in 1ZOH-L3, 2OXX-L4 and 3KXM-L8 having interaction energy as -6.89, -5.37, and -10.48 kcal/mol respectively. Overall, this study will pave way for crystal growth and medicinal chemist to have cleared perceptive about structural properties of CK2 halogenated ligands with new insight on CK2 mutated functional group ligands. Further, it insists us to reuse existing CK2 crystal ligand with more preferable suggested binding contacts in course of new functional groups that lead to anticancer affinity.Communicated by Ramaswamy H. Sarma.
本研究的重点是通过相互作用能分析，了解晶体 CK2 配体中四溴苯并三唑（TBB）衍生物中卤素（X=Br）原子与铰链区氨基酸（VAL45、PHE113、GLU114、VAL116、ASN118）的结合能力。反过来，通过深入了解核心 CK2 配体的稳定性性质：1ZOE-L1、1ZOG-L2、1ZOH-L3、2OXX-L4、2OXY-L5、3KXG-L6、3KXH-L7、3KXM-L8，这些配体有四个溴原子，我们试图通过各种官能团（X=Cl、F、CF、CH、NH、OH、H）取代所有溴原子（X=Br），并计算与氨基酸的结合强度。最稳定的配体存在于取代的 NH 官能团中：1ZOG-L2、1ZOH-L3、2OXX-L4、3KXM-L8 的相互作用能分别为-5.21、-14.87、-6.69 和-11.72 kcal/mol，表明具有较强的结合强度。其次稳定的取代 Cl 官能团配体在 1ZOH-L3、2OXX-L4 和 3KXM-L8 中也起着重要作用，其相互作用能分别为-6.89、-5.37 和-10.48 kcal/mol。总的来说，这项研究为晶体生长和药物化学家提供了一个途径，使他们对 CK2 卤化配体的结构性质有了更清晰的认识，并对 CK2 突变官能团配体有了新的认识。此外，它还促使我们在新的官能团中重新使用现有的 CK2 晶体配体，并选择更理想的建议结合接触，从而提高抗癌亲和力。由 Ramaswamy H. Sarma 传达。
