BMAP27 Case Study

Secondary structure of BMAP27 in aqueous media and force field dependent peptide folding was studied. BMAP27 in aqueous solution displayed an extended conformations and occupied a large conformational space in both force fields (Table 1) during the simulation period of 0.5 s (Fig 1A and 1B). The partial densities of the peptide distribution were broadened owing to the unfolded conformations (Fig 1A and 1B).
Simulations for BMAP27 interaction with zwitterionic and anionic membranes depicted a differential peptide folding and kinetics. Results showed a fast peptide attraction (~ 50-80 ns) followed by slow binding and reorientation (~100-500 ns) on the bilayer surface. The calculated -helical conformation of BMAP27 revealed a significant helical
On the other hand, a relatively larger number of hydrogen bond (H-bond) formation at the N-terminal arginine (R2, R5 and R7) and lysine (K8 and K9) residues was calculated in the DOPG system (Table 2). The mass density profile of the both systems depicted a little variation in the bilayer thickness. The change in thickness was < 5 Å, and a comparatively large water and lipid density change was obtained from the POPC system. The effect of BMAP27 binding on membrane dynamics of the two lipid systems was compared in their average lateral diffusion coefficient (DL) derived from the initial (0-10 ns) and final (490-500 ns) 10 ns time period. In the POPC system, the average DL of 0.016 (± 0.003) x 10-5 cm2 s-1 and 0.008 (± 0.004) x 10-5 cm2 s-1 was calculated for the initial and final states, respectively. The DOPG system depicted a DL of 0.012 (± 0.010) x 10-5 cm2 s-1 and 0.014 (± 0.000) x 10-5 cm2 s-1 for the initial and final conformers, respectively. The significant decrease and negligible change of DL in the POPC and DOPG systems, respectively, indicated a differential BMAP27 membrane absorption and binding mechanism. Substantial difference in the partial densities of peptide distribution and lipid molecules was observed during the period of 0.5 s for the POPC system (Fig 2A). On the contrary, no
In contrast, a bent and restrained helical conformation with the central kink at F10 residue was observed in the LLM system (Fig 3). The helical content of BMAP27 was calculated to be > 60% and < 20% in the simulations for the LLM and TLM models, respectively (S2B Fig). The results closely resemblance the CD spectroscopy findings of its homologous protein in human that shows partial binding and ~10 % helix in mammalian-like membranes as compared to bacterial-like membranes [38]. The number of intermolecular H-bonds were the highest for the helical cationic residues bonding with the lipid phosphate and carboxyl atoms in the TLM and LLM systems, respectively (Table 2). The interaction networks of different lipid components were measured and interpreted during the 0.5 s simulation. In the TLM system, the highest number of H-bonds was yielded by the PC (average ~14.35) followed by PE lipids (average ~3.14). Relatively strong peptide-lipid bonding network was revealed for the anionic PS (average ~16.20) followed by PC lipids (average ~5.81) in the LLM system. In both membrane models a very weak peptide-cholesterol interaction was calculated, which indicated a limited peptide penetration during the 0.5 s simulation (S4 S3 Fig). The peptide COM in the two systems exhibited its membrane surface distribution and penetration. The small intrusion of BMAP27 is characterized by its helix