Deepa Palanisamy, Thirumeignanam Duraisamy
Department of Physics, Manonmaniam Sundaranar University, Tirunelveli, 627 012, India.
Department of Animal Nutrition, Veterinary College and Research Institute, Veterinary and Animal Sciences University, Tirunelveli, 627 358, India.
J Mol Graph Model. 2020 Jun;97:107553. doi: 10.1016/j.jmgm.2020.107553. Epub 2020 Jan 31.
The present study clearly depicts the understanding of the D44 in Plasmodium FKBP35 around the hinge region. To analyse the binding stability of D44 ligand and to understand the role of halogen bond, hydrogen bond interaction formed between the hinge region amino acids: Isoleucine (Ile74), Phenylalanine (Phe54), Aspartic acid (Asp55) Phenylalanine (Phe64),Tyrosine (Tyr100), Tryptophan (TRP 77) and ligand D44 was portrayed specifically through interaction energy calculations at HF, M062X, MP2 level of theories for different basis set (6-311G**, 6-31+G*, LANL2DZ). The investigation will provide an apparent picture regarding the non-covalent interaction that hold the contact of ligand and amino acids in the hinge region and the implication of modelled functional groups (Br, Cl, F, OSO and NH) on ligand, which will help chemist in synthesizing new novel ligands. HOMO, LUMO chart calculated for D44 ligands reveals graphic illustration of orbital's that stimulate for contact. The aim and natural bond orbital analysis identified key contribution of individual hydrogen/halogen bonds that contribute for the binding strength through stabilization energy, ρ and ∇ρ values. Overall this study finds out that the Stability of D44 in Plasmodium FKBP35 was enhanced by the Halogen atom (Br, Cl, F) functional groups; which provide an innovative pathway for the selection of functional groups that opt for the hinge region side chains on the ligand.
本研究清晰地描绘了疟原虫FKBP35中D44在铰链区周围的情况。为了分析D44配体的结合稳定性并了解卤键的作用，通过在HF、M062X、MP2理论水平下针对不同基组（6 - 311G**、6 - 31 + G*、LANL2DZ）进行相互作用能计算，具体描绘了铰链区氨基酸异亮氨酸（Ile74）、苯丙氨酸（Phe54）、天冬氨酸（Asp55）、苯丙氨酸（Phe64）、酪氨酸（Tyr100）、色氨酸（TRP 77）与配体D44之间形成的氢键相互作用。该研究将提供一幅关于在铰链区维持配体与氨基酸接触的非共价相互作用以及配体上建模官能团（Br、Cl、F、OSO和NH）影响的清晰图景，这将有助于化学家合成新的新型配体。为D44配体计算的HOMO、LUMO图揭示了促进接触的轨道的图形说明。目标和自然键轨道分析确定了通过稳定能、ρ和∇ρ值对结合强度有贡献的各个氢/卤键的关键贡献。总体而言，本研究发现疟原虫FKBP35中D44的稳定性通过卤原子（Br、Cl、F）官能团得到增强；这为选择配体上铰链区侧链的官能团提供了一条创新途径。
