By analyzing the arrangement of UL49.5 in the ER membrane, we found that for BoHV-1 protein the fragment R1-E11 was primarily immersed in water environment (Figure and Figure ), whereas the fragment E10-A63 was mainly buried in the hydrophobic part of the ER membrane. The C-terminal fragment of UL49.5 (S64-P66) was immersed in the hydrophilic part of the membrane. The last nine amino acid residues N67-G75 (Figure ) were strongly exposed to the aqueous environment (distance to lipid bilayer center larger than 30 Å see Figure ). The location of this protein in the ER membrane is similar to the previously described location of this protein in the POPC membrane . As in the POPC membrane, the location of the BoHV-1 UL49.5 protein in ER membrane is determined by charged amino acid residues that orient the protein in such a way that the N-terminal and Cterminal fragments are accessible to water molecules (Figure ). Also, similar to the MD calculations for the UL49.5 protein in the POPC membrane, helices 2 and 3 are aligned with each other. Their axes form an angle of 89.43° (SD: 5.30) (Figure ). BoHV-1 at the N-and C-terminus of the transmembrane helix, there are not many charged amino acids (Figure ). It is true that there are charged amino acids at the N-terminal fragment, but this fragment of the protein is very flexible and does not have the function of fixing the protein in the membrane. At the C-terminus, on the other hand, there is only one R61 residue that anchors the protein to the membrane from the luminal site. By analyzing the position of the transmembrane helix (amino-acid residues 37-59) in the ER membrane, it can be seen that the transmembrane (TM) helix is tilted with respect to the Z-axis by 35.51 degrees (SD: 3.99) (Figure ). This TM helix arrangement was not changing significantly throughout the molecular dynamics time. This may be due to the fact that there are a lot of charged amino acid residues in the N-terminal part of the protein, much more than in the protein from BoHV-1. Number of contacts between TM or all amino-acid residues of BoHV-1 or HSV-1 with lipid heads (Figure ) is different for both proteins. BoHV-1 protein forms in total 33% more contacts with lipid bilayer head (on average 18.04 and 13.57 contacts for BoHV-1 and HSV-1, respectively), however this difference drops down to 16% (on average 12.65 and 10.85 contacts for BoHV-1 and HSV-1, respectively) if only amino-acid residues positioned inside the lipid bilayer (average range of distances between amino-acid residues and lipid bilayer center from -20 to 20 Å, Figure and Table ) indicating that outer membrane parts of the BoHV-1 protein tend to stay closer to lipid bilayer and interact with it. It is most likely caused by a higher number of polar residues in BoHV-1. Taking into account that PC:PE:PS lipid head ratio is 27:15:8, so their percentages are 54, 30 and 16, respectively, especially HSV-1 protein tends to form more interactions with PS heads than PE. With almost double the number of PE heads compared to PS ones in membrane composition, it indicates that there is a strong tendency of HSV-1 to interact with charge heads of PS lipids than with polar PC and PE heads.