Solvent Dielectric Effect and Side Chain Mutation on the Structural Stability of Burkholderia cepacia Lipase Active Site: A Quantum Mechanical/Molecular Mechanics Study

Abstract

Quantum mechanical and molecular dynamics methods were used to analyze the structure and stability of neutral and zwitterionic configurations of the extracted active site sequence from a Burkholderia cepacia lipase, histidyl-seryl-glutamin (His86-Ser87-Gln88) and its mutated form, histidyl-cysteyl-glutamin (His86-Cys87-Gln88) in vacuum and different solvents. The effects of solvent dielectric constant, explicit and implicit water molecules and side chain mutation on the structure and stability of this sequence in both neutral and zwitterionic forms are represented. The quantum mechanics computations represent that the relative stability of zwitterionic and neutral configurations depends on the solvent structure and its dielectric constant. Therefore, in vacuum and the considered non-polar solvents, the neutral form of the interested sequences is more stable than the zwitterionic form, while their zwitterionic form is more stable than the neutral form in the aqueous solution and the investigated polar solvents in most cases. However, on the potential energy surfaces calculated, there is a barrier to proton transfer from the positively charged ammonium group to the negatively charged carboxylat group or from the ammonium group to the adjacent carbonyl oxygen and or from side chain oxygen and sulfur to negatively charged carboxylat group. Molecular dynamics simulations (MD) were also performed by using periodic boundary conditions for the zwitterionic configuration of the hydrated molecules in a box of water molecules. The obtained results demonstrated that the presence of explicit water molecules provides the more compact structures of the studied molecules. These simulations also indicated that side chain mutation and replacement of sulfur with oxygen leads to reduction of molecular flexibility and packing.

Functionalized Mesoporous Silica Nanoparticle for Levodopa Delivery: A Combination with SWCNTs

“…The type attracting most attention is the single-wall CNT, which has a diameter deserving the name of "nanotube" of 0.4 to 2 nanometers. [50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65] The length is usually in the order of microns, but singlewall CNT with a length about centimeters have recently released. The extremities of the CNT have usually closed with lids of the graphite sheet.…”

Anti-cancer properties of green Tea Probed viaquantum mechanics calculations

“…Unlike black and oolong tea, green tea production does not involve oxidation of young tea leaves [1][2][3] . Green tea is produced from steaming fresh leaves at high temperatures, thereby inactivating the oxidizing enzymes and leaving the polyphenol content intact [4][5][6][7][8] .…”

The interaction of single walled carbon nanotube (SWCNT) with phospholipids membrane: in point view of solvent effect

“…The choline-containing phospholipids are located mainly in the outer molecular layer .This asymmetric distribution is maintained by an ATP-dependent protein which specifically Trans-locates phosphatidyl-ethanolamine (and phosphatidylserine) to the inside of the plasma membrane [30][31][32][33] .…”