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General information
Name: DESRES-ANTON-10930523 2 µs simulation of an investigational or FDA approved drug molecule binding to a construct of the SARS-CoV-2 trimeric spike protein, no water or ions (alprostadil)
Included proteins: Spike
Uniprot ID: P0DTC2
Species: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) (SARS-CoV-2)
PDB ID: 6VXX
Description: This simulation is part of a series of 50 simulations: 50 2 µs trajectories of FDA approved or investigational drug molecules that in simulation remained bound to a construct of the SARS-CoV-2 trimeric spike protein at positions that might conceivably allosterically disrupt the interaction between these proteins. The small molecule drugs and their initial binding poses were chosen from a combination of molecular dynamics simulation and docking performed using an FDA-investigational drug library. The 50 putative spike protein binding small molecules located at three regions on the spike trimer, a pocket in the RBD whose formation may possibly enhance RBD-RBD interactions in the closed conformation (8 molecules), a pocket between the two RBDs in the closed conformation (29 molecules), and a pocket that involves three RBDs in the closed conformation (13 molecules). The simulations used the Amber ff99SB-ILDN force field for proteins, the CHARMM TIP3P model for water, and the generalized Amber force field for small molecules. The C- and N-peptide termini were capped with amide and acetyl groups respectively. The spike trimer construct was modeled from PDB entries 6VXX and 6VW1, only retaining the RBD and a short region from S1 fusion protein as a minimal system for maintaining a trimer assembly. The system was neutralized and salted with NaCl, with a final concentration of 0.15 M. The interval between frames is 1.2 ns. The simulations were conducted at 310 K in the NPT ensemble.
Extracted from: BioExcel (ID: MCV1900144)
Author: D. E. Shaw Research
Submission date: October 22, 2020
System setup
Ligands:
alprostadil
Membrane composition: None
Solvent type: TIP3P (water was filtered out of the simulation output)
Total number of atoms: 14512
Simulation details
Software and version: Anton supercomputer specific tools None
Forcefield and version: Amber ff99SB-ILDN
Delta : 1.2 ns
Replicates: 1
Accumulated simulation time: 2.0016 µs
References
D. E. Shaw Research. Molecular Dynamics Simulations Related to SARS-CoV-2. D. E. Shaw Research Technical Data, 2020. http://www.deshawresearch.com/resources_sarscov2.html/
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