| Autor: |
Barbosa ED; Departamento de Biofísica e Farmacologia, Universidade Federal do Rio Grande do Norte, Natal 59072-970, Rio Grande do Norte, Brazil., Lima Neto JX; Departamento de Biofísica e Farmacologia, Universidade Federal do Rio Grande do Norte, Natal 59072-970, Rio Grande do Norte, Brazil., Bezerra KS; Departamento de Biofísica e Farmacologia, Universidade Federal do Rio Grande do Norte, Natal 59072-970, Rio Grande do Norte, Brazil., Oliveira JIN; Departamento de Biofísica e Farmacologia, Universidade Federal do Rio Grande do Norte, Natal 59072-970, Rio Grande do Norte, Brazil., Machado LD; Departamento de Física Teórica e Experimental, Universidade Federal do Rio Grande do Norte, Natal 59072-970, Rio Grande do Norte, Brazil., Fulco UL; Departamento de Biofísica e Farmacologia, Universidade Federal do Rio Grande do Norte, Natal 59072-970, Rio Grande do Norte, Brazil. |
| Jazyk: |
angličtina |
| Zdroj: |
The journal of physical chemistry. B [J Phys Chem B] 2021 Dec 02; Vol. 125 (47), pp. 12972-12980. Date of Electronic Publication: 2021 Nov 18. |
| DOI: |
10.1021/acs.jpcb.1c07298 |
| Abstrakt: |
Envenomation via snakebites occurs largely in areas where it is harder to access the hospital. Its mortality rate and sequelae acquired by the survivors symbolize a big challenge for antivenom therapy. In particular, the homologous phospholipase A 2 (Lys49-PLA 2 ) proteins can induce myonecrosis and are not effectively neutralized by current treatments. Thus, by taking advantage of crystallographic structures of Bothrops moojeni Lys49-PLA 2 complexed with VRD (varespladib) and AIN (aspirin), a quantum biochemistry study based on the molecular fractionation with conjugate cap scheme within the density functional theory formalism is performed to unveil these complexes' detailed interaction energies. The calculations revealed that important interactions between ligands and the Lys49-PLA 2 pocket could occur up to a pocket radius of r = 6.5 (5.0 Å) for VRD (AIN), with the total interaction energy of the VRD ligand being higher than that of the AIN ligand, which is well-correlated with the experimental binding affinity. Furthermore, we have identified the role played by the amino acids LYS0069, LYS0049, LEU0005, ILE0009, CYS0029, GLY0030, HIS0048, PRO0018, ALA0019, CYS0045, TYR0052, TYR0022, PRO0125*, and PHE0126* (LYS0069, LYS0049, GLY0032, LEU0002, and LEU0005) in the VRD↔Lys49-PLA 2 (AIN↔Lys49-PLA 2 ) complex. Our simulations are a valuable tool to support the big challenge for neutralizing the damages in victims of snakebites. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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