Dataset of the simulations in the GōMartini 3: From large conformational changes in proteins to environmental bias corrections

This section describes the data files for the nanomechanics of SARS-CoV-2 RBD in complex with a potent nanobody (H11-H4) by GōMartini approach.

(1) The data_4iu3.tar.xz file has all the files necessary to reproduce the pulling simulations of PDB ID 4IU3 using GōMartini methodology. The files are described below.

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https://www.rcsb.org/structure/4iu3

Cohesin-dockerin -X domain complex from Ruminococcus flavefacience

https://github.com/rams-research/OVrCSU

http://pomalab.ippt.pan.pl/GoContactMap/

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4iu3.pdb                                                : All-atoms PDB file

4iu3.map                                                : All-atoms OVrCSU contac map file

A.pdb,B.pdb                                          : All-atoms Structures of Cohesin and Dockering, later referenced as molA and molB

index.ndx                                               : base index file

martini_v3*.itp                                      : Martini3 force field definitions

GoMartini, topology files:

        molA.itp

        molA_exclusions_VirtGoSites.itp

        molB.itp

        molB_exclusions_VirtGoSites.itp

        go-table_VirtGoSites_interface.itp

        go-table_VirtGoSites.itp

        topol.top

GoMartini, GROMACS MDP equilibration and final GRO files:

        Pre-equilibration:

                min.mdp, min.gro

                npt.mdp, npt,gro

                nvt.mdp, nvt.gro

        Equilibration MD run:

                md-corr.log

                md-corr.mdp

                md-corr.edr

                md-corr.gro

                md-corr.tpr

Topology and force field definitions:

        GGG_pull/BB-part-def_VirtGoSites.itp

        GGG_pull/go-table_VirtGoSites.itp

        GGG_pull/index.ndx

        GGG_pull/martini_v3.0.4.itp

        GGG_pull/martini_v3.0_ions.itp

        GGG_pull/martini_v3.0_phospholipids.itp

        GGG_pull/martini_v3.0_solvents.itp

        GGG_pull/molA_exclusions_VirtGoSites.itp

        GGG_pull/molA.itp

        GGG_pull/molB_exclusions_VirtGoSites.itp

        GGG_pull/molB.itp

Pulling MD runs from 100 runs ({1-100}), GROMACS files:

        GGG_pull/md_pull_{1-100}-trajectory-protein.pdb : Trajectory in PDB format

        GGG_pull/md_pull_{1-100}_pullf.xvg                        : force profile

        GGG_pull/md_pull_{1-100}_pullx.xvg                       : distance profile

        GGG_pull/md_pull_{1-100}.log                                  : log files

        GGG_pull/md_pull_{1-100}.edr                                 : EDR files

        GGG_pull/md_pull_{1-100}.tpr                                 : TPR files

2) The data_6zh9_1.tar.xz, data_6zh9_2.tar.xz,  data_6ZH9_GM2.tar.xz, and data_6ZH9_GM3.tar.xz files contain

The dataset comprises a total of 50 replicas, each with a total of 751 snapshots, and the mdp and tpr files, which are located in the CG_Pull/Trajectories folder, for the RBD-H11-H4 complex. The gro, mdp and tpr files for NVT and NPT equilibrations are included.

The force and displacement xvg files for each replica are included in the GC_Pull folder (pullf*.xvg and pullx*.xvg, respectively). The output files from GōMartini are included.

The system consists of a single-domain antibody (i.e. nanobody) and the receptor-binding domain (RBD) portion of the SARS-CoV-2 spike protein. In this regard, the nanobody named H11-H4 and the RBD form a mechanostable protein complex with PDB ID: 6ZH9. The entire system was modeled by the Martini 3 force field. The same protocol as for the XMod-Doc:Coh complex was employed. The GōMartini model requires a total of 715 contacts divided into 404 and 285 for the RBD and the H11-H4 respectively and the protein complex interface was represented by 26 contacts. The value of the dissociation energy of the LJ potentials was set to a value of ε = 15.0 kJ/mol. The dimensions of the water box for the RBD-Nb complex were 16x12x90 nm3 with a 0.15 M NaCl. There were 135,669 CG water beads representing 542,676 water molecules.

To conduct the nanomechanical studies, the positions of RBD residues GLY-526, PRO-527, and  LYS-528 were kept frozen in the z-axis and the coordinates of residues SER-126, SER-127, and LYS-128 in H11-H4 were kept frozen in x- and y-axis, and were chosen for SMD simulation at constant speed.

Two different protocols according to all-atom SMD simulation were considered. i) in data_6zh9_1.tar.xz: Restraints were applied to the backbone atoms of the RBD with a spring contact of kb =1000 kJ/(mol·nm2) to avoid large deformation and the residue in the SMD protocol with velocity equal to 5x10-3 nm/ps was coupled to another harmonic potential with a spring constant equal to 600 kJ/(mol·nm2) and ii) data_6zh9_2.tar.xz: Pulling velocity was equal to 1x10-4 nm/ps was coupled to another harmonic potential with a spring constant equal to 600 kJ/(mol·nm2). 

The supplementary files data_6ZH9_GM2.tar.xz and data_6ZH9_GM3.tar.xz followed a similar protocol as data_6ZH9_2.tar.xz, with the following differences: the box size was set to 10 × 10 × 60 nm, and the spring constant was adjusted to 37.6 kJ/(mol·nm²). For the GōMartini 2 model, the default value of ε = 9.414 kJ/mol was used.

3) The IDP_GoMartini3.tar.gz file has the following folders:

a) Atomistic

The _atomistic_ directory contains subfolders for each of the IDPs tested. Each subdirectory contains the topology for the protein and an initial starting structure. There is also a folder of the mdp files used. In each simulation, the correct temperature as described in the manuscript was applied.

b) Martini

The _martini_ directory contains subfolders for each of the IDPs tested. Each subdirectory contains topology for the corresponding protein model tested, and the starting structure used. The TEMP variable in the mdp files was replaced with the experimentally corresponding temperature in each simulation.

c) Condensate

The _condensate_ directory contains two systems. The artifical IDP (_aIDP_) condensate system of Dzuricky et al. and the short peptides of Abbas et al. (_peptides_)

_aIDP_ has two systems comparing the native and optimised topologies for the phase separation of the aIDP.

_peptides_ contains a single system with topologies for protonated and deprotonated synthetic peptides, as well as the starting structures, and topology files for the differently rescaled protein-water interactions used.

4) The WALPDATA.tar.gz has the following folders:

a) ProteinITPs has all GROMACS itp files for the WALP α-helices – 16, 19, 23, and 27 denoted as WALP16, WALP29, WALP23 and WALP27 as well as the GōMartini inputs

b) mdps and the script for preparing the mebrane for the WALP peptides PrepareMembranePeptideSim.ipynb

5) The BetaSheet_GoMartini.tar.gz file has the following folders:

molecule_0.itp   is the itp file for beta strand 1.molecule_1.itp   is the itp file for beta strand 2.

martini.itp      is the Martini forcefield itp used.

rCSU.map         is the rCSU map generated.OV.map           is the OV map generated.

GoMartini files:

    molecule_0_exclusions_VirtGoSites.itp     molecule_0_BB-part-def_VirtGoSites.itp    molecule_0_go-table_IDPsolubility.itp      molecule_0_go-table_VirtGoSites.itp     molecule_0_go4view_harm.itp      BB-part-def_VirtGoSites.itp     go-table_VirtGoSites.itp 

mdp files used:

    min.mdp     rel_310.mdp     prod_310.mdp 

rada_sheet_canonical.pdb     is the PDB file of the AA RADA16 structure.rada_cg.pdb                  is the PDB file of the Martini RADA16 structure.

Inside folder Negative_Control is the topology file forthe system with no structural or interaction bias.

Inside folder GoVirt_Bias is the topology file forthe system with a GoMartini model applied between thetwo strands.

Inside folder Scaled_Water is the topology file forthe system with GoVirt water interaction scaling.

6) The md_inputs_go_IDPs_PETER.tar.gz file has the following folders:

Directories "a1", "hst5", and "pnt" contain the input files for proteins with Go potentials. And in the "controls" directory, input files for the same proteins, without Go potentials.

To run the simulations, the user can run the following commands:

gmx grompp -f md.mdp -p topol.top -c pre_md.gro -o mdgmx mdrun -s md.tpr -deffnm md

Additionally, atomistic structures are available in .gro format - {protein}_atomistic.gro

7) The repository_Hafez.zip 

In the folders 1AOH, 1TIT, 1UBQ, 3W0K, AQP1, and Ist2, you will find the necessary files (ITP, MDP, and GRO) to repeat the simulations.

In the Martini3FF folder, you can find the MARTINI3 force field files.

8) The Hairpin-M3-15.tar.xz and Hairpin-M2.tar.xz and Hairpin-M2-15.tar.xz 

contains the information mdp, itp and trajectories generated for the study of folding simulation with GoMartini implemented in 2017 and the latest implementation on top of the Martini 3 force field.

The Hairpin-M2, Hairpin-M2-15, and Hairpin-M3-15 folders contain all the necessary files to reproduce the pulling simulations of PDB ID 1GB1 (a novel, highly stable fold of the immunoglobulin binding domain of streptococcal protein G) using the GōMartini 2 and GōMartini 3 methodologies, respectively.

Each folder contains:

A.pdb: All-atom PDB file of the unfolded structure.B.pdb: All-atom PDB file of the folded structure.A-CG.pdb: Martini coarse-grained representation of the unfolded structure.B-CG.pdb: Martini coarse-grained representation of the folded structure.A-GC.gro: GROMACS format file of the unfolded structure.B-GC.gro: GROMACS format file of the folded structure.system.top: Topology file.

Force Fields and Topologies:GōMartini 2:martini_v2.2.itp: Martini 2 force field for proteins.martiniv2.2_ions.itp: Martini 2 force field for ions.Protein_A.itp: GōMartini 2 topology for the folded structure.Protein_A_unfolded.itp: GōMartini 2 topology for the unfolded structure.

GōMartini 3:martini_v3.0.0.itp: Martini 3 force field for proteins.martini_v3.0.0_ions_v1.itp: Martini 3 force field for ions.martini_v3.0.0_solvents_v1.itp: Martini 3 force field for solvents.go_martini.itp: GōMartini 3 topology for the folded structure.go_martini_unfold.itp: GōMartini 3 topology for the unfolded structure.go_molecule1.itp: Additional GōMartini 3 topology file.A.map: Contact map for the unfolded structure.B.map: Contact map for the folded structure.

GROMACS Files for Equilibration and MD Runs:

Equilibration:minimization.mdp, minimization.gro: Files for energy minimization.nvt.mdp, nvt.gro, nvt.xtc, nvt.tpr: Files for NVT equilibration.npt.mdp, npt.gro, npt.xtc, npt.tpr, npt_dry.tpr: Files for NPT equilibration (dry simulations without waters or ions).

Folding MD Runs:dynamic.mdp: File for folding molecular dynamics runs.Folding MD Runs (1-100):MD/hairpin-M2_fit.xtc*: Trajectories (without waters or ions, ε = 9.414 kJ/mol).MD/hairpin-M2-15_fit*.xtc*: Trajectories (without waters or ions, ε = 15.0 kJ/mol).

MD/hairpin-CG-M3-_fit*.xtc: Trajectories (without waters or ions, ε = 15.0 kJ/mol).

Data Analysis Scripts:MD/Distances_native_WT.ipynb: Jupyter notebook for backbone distance analysis.MD/all_native_graphs.ipynb: Jupyter notebook for native contact analysis.MD/total_contacts_column.ipynb: Python script for contact statistics.