قادر حسین زاده

• Introduction Because of increased transcript and protein level of placenta growth factor (PlGF) in cancerous cells, hampering of PlGF or its receptor could prevent the cancer cell growth [1-3]. Due to the beneficial characteristics of Nanobodies (Nb), they are good candidates for blocking of growth factors [4]. • Experimental / Methods In this regards, the main objective of this research is to design an Nb with high binding affinity against PlGF based on antibody engineering methods [5]. by using molecular dynamics (MD) simulation. The all atom MD simulations were carried out using the GROMACS 5.1.2 MD package with GROMOS96 43a1 force field. The complex of PlGF (PDB: 1FZV) and Nb (PDB: 4W6Y) was used for MD simulations. • Results and discussion In MD simulations, by investigation the contact area and interactions between PlGF and Nb with COCOMAPS analyse, the LYS43 residue of Nb was selected for mutagenesis because of its unfavourable electrostatic interaction (repulsion) with ARG117 and HIS59 residues of PlGF. Then, two single mutation of LYS43 to GLU and LYS43 to ASP were proposed which labelled as V1 and V2 variants, respectively. • Conclusion Among these variants, LYS43 to GLU mutation (V1 variant) shows good binding affinity enhancement and structural stability, in comparison to wild type Nanobodie (V0 variant). Enhancement mechanism for R52E variant is reduction of distance of Nb and PlGF, increasing of contact area between Nb and PlGF and formation of new suitable interactions between them Nb and PlGF. Although, LYS43 to ASP in V2 variant shows improved binding energy, however, this mutation causes some structure fluctuation and instability in the Nb structure. The results of this work could be useful in designing of high affinity Nb against the cancer growth factors.