## 3 Results and Discussion  
### PES Interactions with Human Serum Proteins  
When blood encounters foreign materials, particularly those lacking hemocomputable top layers, it triggers a cascade of interconnected reactions. These include protein adsorption, blood protein activation, platelet adhesion, complement activation, and the onset of  
Figure 1: Structures, stick view (with energy minimization), and dipole orientation of polyethersulfone (PES) and zwitterion chains (MMP and MPC). blood dots and thrombus formation, culminating in the development of a fibrin matrix [44]. The subsequent accumulation of a protein cake layer on the dialyzer membrane surface can hinder the device's functionality, potentially leading to various adverse effects and reducing the device's lifespan. Given these implications, a thorough examination of protein interactions and adsorption on membrane surfaces becomes imperative to enhance membrane hemocompatibility. To further elucidate the underlying mechanisms and interactions that contribute to these phenomena, our study has looked into the interactions between the PES membrane and protein chains, which are pivotal in understanding fouling. The fouling on the PES membrane is primarily attributed to two major interactions: Hydrophilic interactions between certain amino acid residues and the PES membrane. Hydrophobic interactions are caused by protein chains with the PES membrane. Furthermore, the aqueous environment of the bloodstream, with its varying composition, can influence the behavior of amino acids. This variation can lead to differential binding affinities of proteins to the membrane, resulting in competitive binding scenarios. In our research, we have delved into these competitive binding dynamics, providing insights into how different proteins might compete for binding sites on the membrane, influenced by the specific amino acid residues and their interactions. Molecular modeling has become a valuable and essential tool to medicinal chemists and biomaterial advances as it could effectively estimate the binding sites and binding energy of the protein-ligand complexes [45; 46]. In this research, we utilized molecular docking to investigate both pristine and zwitterion-grafted PES membranes in interaction with three critical human serum proteins: HSA, FB, and Tr. We aimed to assess the impact of zwitterion grafting (as depicted in Figure 1) on PES hemocompatibility and to further analyze how dipole orientation influences affinity energy and the dynamics of membrane-protein interactions. The molecular docking results of the PES membrane model with the active sites of different human serum proteins, including HSA, FB, and Tr, revealed two significant interactions: (1) polar interaction between the etheric and SO\({}_{2}\) groups of PES and the hydrophilic parts of proteins; and (2) apolar or hydrophobic interactions between protein constituents and phenyl groups in the PES structure. As shown in Figure 2, according to docking of the PES structure and the HSA, FB, and Tractive sites, the SO\({}_{2}\) groups interact with the hydrophilic pockets of proteins as a hydrophilic contact with Arg209, Trp33, Ser189, and Gly190 amino acids. The residues Asp61, Cyc28, Ser31, Ser47, and Arg50 are responsible for other hydrogen bonds. The Phe228, Ala213, Leu327, Leu437, Leu481, Gly328, Leu331, Ala210, Val216, Ala350, Val482, Val215, Leu481, Val74, Ala27, Gly28, Trp33, Ala59, Leu72, Pro70, Leu66, Leu293, Leu294, Gly190, Ala191, Phe186, Tyr188, and Thr181 pockets that surround the phenyl groups in the PES model are also considered hydrophobic interactions of this molecule. Therefore, PES has more hydrophobic interactions than hydrophilic ones and fits better in the hydrophobic moiety. Docking analysis showed that PES ligand interactions with albumin protein had maximum binding energies of \(-10.3\) kcal/mol, while interactions with FB and Tr proteins had binding energies of \(-8.5\) kcal/mol and \(-9.2\) kcal/mol, respectively.