Molecular simulation of N-acetylneuraminic acid analogs and molecular dynamics studies of cholera toxin-Neu5Gc complex

Abstract

Cholera toxin (CT) is an AB5 protein complex secreted by the pathogen Vibrio cholera, which is responsible for cholera infection. N-acetylneuraminic acid (NeuNAc) is a derivative of neuraminic acid with nine-carbon backbone. NeuNAc is distributed on the cell surface mainly located in the terminal components of glycoconjugates, and also plays an important role in cell-cell interaction. In our current study, molecular docking and molecular dynamic (MD) simulations were implemented to identify the potent NeuNAc analogs with high-inhibitory activity against CT protein. Thirty-four NeuNAc analogs, modified in different positions C-1/C-2/C-4/C-5/C-7/C-8/C-9, were modeled and docked against the active site of CT protein. Among the 34 NeuNAc analogs, the analog Neu5Gc shows the least extra precision glide score of -9.52 and glide energy of -44.71 kcal/mol. NeuNAc analogs block the CT active site residues HIS:13, ASN:90, LYS:91, GLN:56, GLN:61, and TRP:88 through intermolecular hydrogen bonding. The MD simulation for CT-Neu5Gc docking complex was performed using Desmond. MD simulation of CT-Neu5Gc complex reveals the stable nature of docking interaction.

Molecular Dynamics Simulation of Cholera Toxin A-1 Polypeptide

“…The hydrophobic residues present at the end of the polypeptide chain are proline and tryptophan but the CTA1 is also strongly hydrophilic which has been proved from water of crystallization present in the crystal structure [7,11]. The cholera toxin simulation at 283, 310 and 323 K showed a mean total SASA of 111 nm 2 , which was exposed to the solvent in the system.…”

“…The most striking architectural feature of the AB 5 toxin is the presence of a central pore or channel that runs along the 5-fold axis of the B5 assembly, forming a ring-like structure [2,6]. The B-subunit is the binding domain; it binds to monosialotetrahexosyl ganglioside (GM1) of the plasma membrane of the host cell [7][8][9]. The A-subunit (CT-A, MW ~ 27,400) is the enzymatic domain [10,11], it contains 240 amino acid residues.…”

Computational insight of dexamethasone against potential targets of SARS-CoV-2

“…MD simulations were carried out using the Desmond software. The optimized potentials for the liquid simulations OPLS-2005 force field were used in this system to determine the receptors interactions with Dex, which was solvated with the simple point charged (TIP-3P) water model (Blessy & Sharmila, 2015 ; Jorgensen et al., 1983 ). The orthorhombic water box was used to create a 10 Å buffer region between the atoms on the receptors and box sides.…”

Design, sythesis and evaluation of a series of 3- or 4-alkoxy substituted phenoxy derivatives as PPARs agonists

“…The operation was mainly conducted on well-prepared structures in several phases [38]. Initially, a model system for generating a solvated system was built with the solvent model set to predefined SPC [33], box shape to orthorhombic and box size calculation to Buffer method through the System Builder panel [39, 40]. The protein was reoriented to minimize the box volume.…”

“…The checkfile was used to restart the simulation if interrupted and should be saved infrequently. Furthermore, the stage to relax model system before simulation was critical in case that the model system built by the System Builder was not optimal [33]. …”