Korlyukov Alexander A, Malinska Maura, Vologzhanina Anna V, Goizman Mikhail S, Trzybinski Damian, Wozniak Krzysztof
A. N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, Vavilov St. 28, Moscow 119991, Russian Federation.
Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, Żwirki i Wigury 101, Warszawa 02089, Poland.
IUCrJ. 2020 Jan 1;7(Pt 1):71-82. doi: 10.1107/S2052252519014416.
High-resolution single-crystal X-ray measurements of the monoclinic polymorph of bicalutamide and the aspherical atom databank approach have served as a basis for a reconstruction of the charge density distribution of the drug and its androgen receptor (AR) and albumin complexes. The contributions of various types of intermolecular interactions to the total crystal energy or ligand:AR energy were estimated. The cyan and amide groups secured the ligand placement in the albumin (Lys-137) and the AR binding pocket (Leu-704, Asn-705, Arg-752), and also determined the packing of the small-molecule crystals. The total electrostatic interaction energy on average was -230 kJ mol, comparable with the electrostatic lattice energy of the monoclinic bicalutamide polymorph. This is the result of similar distributions of electropositive and electronegative regions on the experimental and theoretical molecular electrostatic potential maps despite differences in molecular conformations. In general, bicalutamide interacted with the studied proteins with similar electrostatic interaction energies and adjusted its conformation and electrostatic potential to fit the binding pocket in such a way as to enhance the interactions, hydrogen bonds and π⋯π stacking.
比卡鲁胺单斜晶型的高分辨率单晶X射线测量以及非球面原子数据库方法，为重建该药物及其雄激素受体（AR）和白蛋白复合物的电荷密度分布奠定了基础。估算了各种类型分子间相互作用对总晶体能量或配体：AR能量的贡献。氰基和酰胺基团确保了配体在白蛋白（Lys-137）和AR结合口袋（Leu-704、Asn-705、Arg-752）中的位置，同时也决定了小分子晶体的堆积方式。平均总静电相互作用能为-230 kJ mol，与单斜比卡鲁胺多晶型的静电晶格能相当。这是由于尽管分子构象存在差异，但实验和理论分子静电势图上正电和负电区域的分布相似。总体而言，比卡鲁胺与所研究蛋白质的静电相互作用能相似，并调整其构象和静电势以适应结合口袋，从而增强相互作用、氢键和π⋯π堆积。
