Molecular Dynamics Simulation of PASylated G-CSF and Proposing a Modified PAS String Sequence in order to Improve Drug’s Properties

PASylation is a new and effective way to increase the half-life of pharmaceutical proteins. This method is an alternative of PEGylaion and uses the natural polymers of Proline, Alanine, and Serine (PAS) amino acids in its structure. In this paper, we have studied the pharmacokinetic properties of PASylated Granulocyte-colony stimulating factor (G-CSF) using Molecular Dynamics (MD) simulation for three different PAS strings length 210, 420 and 630. We studied several important mechanical quantities involving in enhancing half-life time of the conjugated protein like root-mean-square distance (RMSD), hydrodynamic volume, protein total energy and its hydrophilicity and we found out volume expansion, increase in hydrophilicity amount and coil structure in PASylation are main mechanical properties influencing half-life time. We also found out that RMSD will be modified by PASylation while energy level shows erratic behavior examining the mentioned residues properties, we have also offered a modified sequence for PAS string according to the importance of different parameters in PAS string’s function.