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This is the simulation data set for the manuscript: Arvelo DM, Comer J, Schmit J, Garcia R (2024) Interfacial water is separated from a hydrophobic silica surface by a gap of 1.2 nm. ACS Nano 18:18683–18692. https://doi.org/10.1021/acsnano.4c05689 This data set includes all files needed to run and analyze the simulations described in the this manuscript in the molecular dynamics software NAMD, as well as the output of the simulations. LAMMPS input files for the ReaxFF simulations are also included. The files are organized into directories corresponding to the figures of the main text and supporting information. They include molecular model structure files (NAMD psf or LAMMPS data), force field parameter files (in CHARMM format or ReaxFF format), initial atomic coordinates (pdb format), NAMD or LAMMPS configuration files, Colvars configuration files, NAMD or LAMMPS log files, and output including restart files (in binary NAMD format) and trajectories in dcd format (downsampled with a stride of 100 to 20 ns per frame). Analysis is controlled by shell scripts (Bash-compatible) that call VMD Tcl scripts or python scripts. These scripts and their output are also included. Version: 1.0. Figure5AC: Simulation of pentadecane on a 5 chains/nm^2 OTS layer. Figure5B_FigureS7: Calculation of force profile for an SiO2 tip asperity model using adaptive biasing force. Systems: octane with 5 chains/nm^2 OTS, octane with 4 chains/nm^2 OTS, decane with 5 chains/nm^2 OTS, water with 5 chains/nm^2 OTS. FigureS6: Simulations showing the effect of octadecane on the structure of the OTS layer for 3 and 5 chains/nm^2 densities. FigureS8: Calculation of the adsorption free energy of tetracosane (C24) at the OTS–water interface using ABF. FigureS9: Python script for estimating the critical concentration to form an alkane layer at the OTS–water interface using the mean-field Ising model. FigureS10: ReaxFF simulation and modeling to create the silanol-terminated amorphous silica model of an AFM tip asperity. FigureS11: Molecular dynamics simulations showing spontaneous assembly of twelve or twenty-four tetracosane (C24) molecules at the interface between water and the alkyl groups of an OTS-conjugated silica surface. 

Binding configuration of a de novo stapled peptide on SARS-CoV-2 spike protein, as predicted by molecular simulation. Stapled residues enhance peptide stability while interacting residues engage key amino acids on the protein receptor-binding domain. 

Molecular dynamics simulations show that thiol-containing capping agents for silver nanoparticles, such as mercaptohexanol and lipoic acid, spontaneously assemble into dense aggregates at the silver–water interface. 

The dataset provided for the manuscript entitled "De novo design of a stapled peptide targeting SARS-CoV-2 spike protein receptor-binding domain" encompasses all the required files to execute and analyze simulations of a designed stapled peptide (Pep 39) attached to spike protein receptor binding domain in the most stable binding configuration, illustrated in Figure 3 of the paper. The dataset is composed of molecular model structure files in NAMD psf format, force field parameter files in CHARMM format, initial atomic coordinates in PDB format, NAMD configuration files, NAMD output files (which consist of restart files in binary NAMD format), and trajectories in dcd format (downsampled to 10 ns per frame). To manage the analysis, there are shell scripts (that work with Bash) that invoke VMD Tcl scripts. These scripts and their output are also contained in the dataset. 

Proteins involved in immune checkpoint pathways, such as CTLA4, PD1, and PD-L1, have become important targets for cancer immunotherapy; however, development of small molecule drugs targeting these pathways has proven difficult due to the nature of their protein–protein interfaces. Here, using a hierarchy of computational techniques, we design a cyclic peptide that binds CTLA4 and follow this with experimental verification of binding and biological activity, using bio-layer interferometry, cell culture, and a mouse tumor model. Beginning from a template excised from the X-ray structure of the CTLA4:B7-2 complex, we generate several peptide sequences using flexible docking and modeling steps. These peptides are cyclized head-to-tail to improve structural and proteolytic stability and screened using molecular dynamics simulation and MM-GBSA calculation. The standard binding free energies for shortlisted peptides are then calculated in explicit-solvent simulation using a rigorous multistep technique. The most promising peptide, cyc(EIDTVLTPTGWVAKRYS), yields the standard free energy −6.6 ± 3.5 kcal mol^−1, which corresponds to a dissociation constant of ∼15 μmol L^−1. The binding affinity of this peptide for CTLA4 is measured experimentally (31 ± 4 μmol L^−1) using bio-layer interferometry. Treatment with this peptide inhibited tumor growth in a co-culture of Lewis lung carcinoma (LLC) cells and antigen primed T cells, as well as in mice with an orthotropic Lewis lung carcinoma allograft model. 

This data set for the manuscript entitled "Computational Design of a Cyclic Peptide that Inhibits the CTLA4 Immune Checkpoint Pathway" includes all files needed to run and analyze the simulations of a designed cyclic peptide (Peptide 16) bound to CTLA4 in the putative most stable binding configuration, which is detailed in Figure 6 of the paper. These files include molecular model structure files (NAMD psf), force field parameter files (in CHARMM format), initial atomic coordinates (pdb format), NAMD configuration files, NAMD output including restart files (in binary NAMD format) and trajectories in dcd format (downsampled to 10 ns per frame). Analysis is controlled by shell scripts (Bash-compatible) that call VMD Tcl scripts. These scripts and their output are also included. Version: 1.0 Conventions Used in These Files =============================== Structure Files ---------------- - ctla4_P16_wat.psf (original NAMD (XPLOR?) format psf file including atom details (type, charge, mass), as well as definitions of bonds, angles, dihedrals, and impropers for each dipeptide.) - ctla4_P16.pdb (initial coordinates before equilibration) - repart_*.psf (same as the above psf files, but the masses of non-water hydrogen atoms have been repartitioned by VMD script repartitionMass.tcl) - rest*.pdb (same as the above pdb files, but atoms have been marked for restraints in NAMD. These files are generated by doPrep.sh, with restraints applied to different atoms.) Force Field Parameters ---------------------- CHARMM format parameter files: - par_all36m_prot.prm (CHARMM36m FF for proteins) - toppar_water_ions_prot.str (CHARMM water and ions with NBFIX parameters needed for protein and others commented out) Template NAMD Configuration Files --------------------------------- These contain the most commonly used simulation parameters. They are called by the other NAMD configuration files (which are in the namd/ subdirectory): - template_min.namd (minimization) - template_rest.namd (NPT equilibration with different parts of the protein restrained) - template_prod.namd (for the long production simulations) Minimization ------------- - namd/min_*.0.namd Restraints ------------- - namd/rest_*.0.namd (both CTLA4 binding site and peptide atoms are restrained) - namd/rest_*.1.namd (CA atoms of CTLA4 and all atoms of the peptide are restrained) - namd/rest_*.2.namd (all atoms of only the peptide are restrained) - namd/rest_*.3.namd (only CA atoms of only the peptide are restrained) - namd/rest_*.4.namd (no atoms are restrained) Production ------------- - namd/pro_*.{D,E,F}.0.namd Analysis ------------- - interaction.sh (Shell script for running analysis with VMD) - calcSeparationNearestAtom.tcl (Calculate the separation between two selections, taking the shortest distance between any pair of atoms spanning the two selections. Accounts for (orthogonal) periodic boundary conditions.) - useful.tcl (VMD Tcl script with a library of useful procs, used by the script above) - sep_*.dat (Output of the above analysis containing rows with two columns: time in nanoseconds and minimum distance in Å) Scripts ------- Files with the .sh extension can be found throughout. These usually provide the highest level control for submission of simulations and analysis. Look to these as a guide to what is happening. 

Interfacial water participates in a wide range of phenomena involving graphite, graphite-like and 2D material interfaces. Recently, several high-spatial resolution experiments have questioned the existence of hydration layers on graphite, graphite-like and 2D material surfaces. Here, 3D AFM was applied to follow in real-time and with atomic-scale depth resolution the evolution of graphite–water interfaces. Pristine graphite surfaces upon immersion in water showed the presence of several hydration layers separated by a distance of 0.3 nm. Those layers were short-lived. After several minutes, the interlayer distance increased to 0.45 nm. At longer immersion times (∼50 min) we observed the formation of a third layer. An interlayer distance of 0.45 nm characterizes the layering of predominantly alkane-like hydrocarbons. Molecular dynamics calculations supported the experimental observations. The replacement of water molecules by hydrocarbons on graphite is spontaneous. It happens whenever the graphite–water volume is exposed to air.