Outer membrane protein A (OmpA) is an essential part of the Gram‑negative bacterial outer membrane, which is essential in the stability of the membrane, the development of biofilm, and resistance to antibiotics. This is a detailed computational analysis involving the use of molecular dynamics (MD) simulations with GROMACS to examine using simulations in a lipid bilayer the structural dynamics, stability, and functional implications of Escherichia coli OmpA. We studied the conformational dynamics, membrane integration patterns, networks of hydrogen bonding, and structural stability of OmpA in physiological conditions through 200 nanoseconds of all‑atom MD dynamics. Root mean square deviation (RMSD) was analyzed and showed that, on average the protein remained stable in conformation after 50 ns with average values of 2.8 ± 0.4 A. Root Mean square fluctuation (RMSF) analysis helped locate regions of the protein that are highly flexible (residues 160‑180) with fluctuation greater than 4.5 A and the transmembrane 2‑barrel domain was rigid (RMSF < 1.5 A). Measurement of radius of gyration was a sign of compact protein structure (17.2 ± 0.3 A) during the simulation. Analysis of secondary structure indicated that 43 percent of the 3D structure was also maintained with few transitions of 3D structures to 43% 3D structure. The analysis of hydrogen bonds showed that there were an average of 185 hydrogen bonds and a standard deviation of 15 intramolecular hydrogen bonds that forms the structure. Calculation of solvent accessible surface area revealed that hydrophobic residues (62) were mostly exposed to the lipid environment with the hydrophilic residues (38) being exposed to the aqueous environment. Three main motion modes with 68% of the total structural variance were obtained by principal component analysis. Analysis of free energy landscape showed that there are two conformational basins which are stable with energy barriers of 4.2 kcal/mol. These results not only give molecular‑level information on the correlation between OmpA structure‑function relationships, but also provide potential antimicrobial drug targets against Gram‑negative pathogens.
ISSN-online 2360-2473 / ISSN-print 1223-0472
