#TITLE_ALTERNATIVE#

• Main Author: SEKAR HUMANI ( NIM : 20910004)Pembimbing :Dr. Muhamad Abdulkadir Martoprawiro, TITIS
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/19568
• Institution: Institut Teknologi Bandung

Nimotuzumab is a humanized monoclonal antibody (mAb) that its uses has more <br /> <br /> <br /> <br /> <br /> advantages when compared with another mAb that targeting RGFR, because it does <br /> <br /> <br /> <br /> <br /> not cause side effects such as skin rash. The combination with radiotherapy shown to <br /> <br /> <br /> <br /> <br /> improve the therapeutic effect, therefore nimotuzumab had been developed as a <br /> <br /> <br /> <br /> <br /> radiopharmaceutical therapy. In preparation, nimotuzumab often conditioned in a <br /> <br /> <br /> <br /> <br /> various of environments with a variation of pH, temperature and the presence of other <br /> <br /> <br /> <br /> <br /> compounds. In this research, molecular dynamics simulations have been carried out <br /> <br /> <br /> <br /> <br /> to study the structure of nimotuzumab due to the effect of temperature, and also <br /> <br /> <br /> <br /> <br /> steered molecular dynamics (SMD) simulation to study the stability of nimotuzumab <br /> <br /> <br /> <br /> <br /> as a result of external forces. Simulations were performed using the Not Just Another <br /> <br /> <br /> <br /> <br /> Molecular Dynamic (NAMD) program and analysis was performed with the Visual <br /> <br /> <br /> <br /> <br /> Molecular Dynamics (VMD) program. From the analysis of Root Mean Square <br /> <br /> <br /> <br /> <br /> Displacement (RMSD) over a span of molecular dynamics simulations for 900 ps, <br /> <br /> <br /> <br /> <br /> RMSD values obtained at temperatures of 277 K, 310 K, 353 K and 373 K are 2,37; <br /> <br /> <br /> <br /> <br /> 2,50; 2,46 and 2,53 respectively. Analysis of stability per residue on the heavy chain <br /> <br /> <br /> <br /> <br /> showed that the active site CDR3 region that is at residues numbered 98 (tryptophan) <br /> <br /> <br /> <br /> <br /> and 99 (phenyl alanine) has the biggest conformational changes. On the light chain, <br /> <br /> <br /> <br /> <br /> the changes occur at residues numbered 1 (aspartat), 127 (serin), and 186 (tyrosine), <br /> <br /> <br /> <br /> <br /> that none of that residues is a part of active site or CDRs region from the light chain. <br /> <br /> <br /> <br /> <br /> Steered Molecular Dynamics (SMD) simulation were carried out by fixing the Nterminal <br /> <br /> <br /> <br /> <br /> end of the heavy chain and applying external forces to the C-terminal end. <br /> <br /> <br /> <br /> <br /> The pulling made at a constant velocity of 0.5 Å/ps. Force peak arising at the start of <br /> <br /> <br /> <br /> <br /> the unfolding process is 1226 pN. This force allegedly caused by the rupture of <br /> <br /> <br /> <br /> <br /> hydrogen bonds between heavy chain residues VAL211 and heavy chain residues <br /> <br /> <br /> <br /> <br /> TYR 194.