Understanding the potency of malarial ligand (D44) in plasmodium FKBP35 and modelled halogen atom (Br, Cl, F) functional groups

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, O=S=O and NH2) 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, rho and del(2)(rho) 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. (C) 2020 Elsevier Inc. All rights reserved.