The evolution of the spike protein and hACE2 interface of SARS-CoV-2 omicron variants determined by hydrogen bond formation

Please cite:
Yu-Yuan Yang, Yufeng Jane Tseng, The evolution of the spike protein and hACE2 interface of SARS-CoV-2 omicron variants determined by hydrogen bond formation, Briefings in Functional Genomics, 2023;, elac053, https://doi.org/10.1093/bfgp/elac053

Analysis

All analysis are in Jupyter notebook files.
Root path: ./Analysis/
Gromacs_RMSF.ipynb: RMSF analysis file.
Gromacs_data_wTIME.ipynb: root mean squre deviation (RMSD)/Radius of gyration (Rg)/Number of hydrogen bonds and pairs(HB-pairs)/correlation between hydrogen bonds and pairs (corr-HB) over time.
Gromacs_distribution.ipynb: distribution of distance and angle of hydrogen bonds.
Gromacs_equilibrium.ipynb: energy/temperature/pressure/density in equilibrium process (energy minimization/NVT/NPT).
Gromacs_features_clustering.ipynb: using molecular dynamics features for clustering into different variants.
Gromacs_hbac_fitting.ipynb: analaysis of autocorrelation of hydrogen bonds (fitting, calculating relaxation time of hydrogen bonds, and so on).
VariantsFreqVaccPlot.ipynb: integrate multiple sources public health data (proportion of vaccinated individuals/variant frequency) into single plot.

Data

Data for analysis (from public health resources or molecular dynamics).
Root path: ./Data/

gromacs parameter files

Path: ./Data/gromacs_mdp
ions.mdp: parameter file when adding ions.
md.mdp: parameter file when performing molecular dynamics for 100 ns.
minim.mdp: parameter file when performing energy minimization (EM).
npt.mdp: parameter file when perfomring equilibrium in normal pressure temperature (NPT).
nvt.mdp: parameter file when perfomring equilibrium in normal volume temperature (NVT).

metadata

Path: ./Data/metadata
CoVariants_data: public health data from CoVariants (about variant frequency).
Owid_data: public health data from Our World in Data (about proportion of vaccinated individuals).
md_tidydata: tidy data of molecular dynamics data.

ComparisonOfVariants.xlsx: All tidy data here.
ComparisonOfVariants_numeric.csv: Numeric tidy data for further analysis (e.g. clustering).
ComparisonOfVariants_wMutual_numeric.csv: Numeric tidy data for further analysis (e.g. clustering). Mutual residues among different PDB model were selected in analysis of RMSD/Rg so that the deviation from different PDB can be reduced.
RMSF.csv: RMSF data for following analysis.

raw data

Path: ./Data/rawdata

Molecular dyanmics (MD) results

variants_6m0j: WT/alpha/beta/gamma/delta/delta plus/epsilon/gamma/lambda/mu/omicron BA.1, BA.2, BA.2.12.1, BA.4/5.
variants_7a91: WT/alpha/beta/gamma/delta/delta plus/epsilon/gamma/lambda/mu/omicron BA.1, BA.2, BA.2.12.1, BA.4/5.
variants_7mjn: alpha.
variants_7v80: beta.
variants_7v84: gamma.
variants_7v8b: delta.

Each folder contains the following items:

6m0j_WT_afterMD_dimplot: Ligplot+ dimplot with chord plot by python3 script here (with after MD structure).
6m0j_WT_beforeMD_dimplot: Ligplot+ dimplot with chord plot by python3 script here (with before MD structure).
2dproj.xvg: PCA analysis for trajectory.
6m0j_WT_afterMD.pdb: initial structure before MD.
6m0j_WT_beforeMD.pdb: final structure after MD.
density_npt.xvg: denesity over time in NPT.
gyrate.xvg: Rg over time.
gyrate_mutual.xvg: Rg over time with mutual residues among 6m0j, 7a91, 7mjn, 7v80, 7v84, 7v8b.
hbac.xvg: autocorrelation of hydrogen bonds between hACE2 and S1RBD.
hbang.xvg: distribution of the angle of hydrogen bonds.
hbdist.xvg: distribution of the distance of hydrogen bonds.
hbnum.xvg: number of hydrogen bonds and pairs over time.
md_protein.xtc: compressed trajectory of 100 ns MD.
potential_em.xvg: energy over time in EM.
pressure_npt.xvg: pressure over time in NPT.
rmsd.xvg: RMSD over time.
rmsd_mutual.xvg: RMSD over time with mutual residues among 6m0j, 7a91, 7mjn, 7v80, 7v84, 7v8b.
rmsf_S1RBD.xvg: RMSF in S1RBD regions.
rmsf_hACE2.xvg: RMSF in hACE2 regions.
temperature_nvt.xvg: temperature over time in NVT.

pdb input

All pdb input for whole molecular dynamics procedure were backuped in ./Data/rawdata/pdb_input.

Structural Analysis Tools

A python 3 self-defined packaged for this study, which might be used in analysis.
Root path: ./StructuralAnalysisTools

Visualization

Figures were generated from analysis including graphical abstract, structrual view, MD results over time, fitting curves, ...
Root path: ./Visualization/

illustration

illu/COVID_variants_v*.png: mutations information in different PDBs (* is the version number).
illu/MyCOVID_Project_Workflow_v*.png: graphical abstract of my analysis (* is the version number).

other plots

DimChordplot: chord plot before and after MD in different PDB models/in different variants.
MD: molecular dyanmics results.
AngleDistribution.png / CorrBetweHBandContac.png / DistDistribution_focus.png / DistDistribution_raw.png / Equilibrium_6m0j.png / Equilibrium_7a91.png / Equilibrium_groundtrue.png / HBautocorr.png / HBnum.png / HBnum35.png / RMSD.png / RMSD_mutual.png / RMSF.png / RadiusOfGyration.png / RadiusOfGyration_mutual.png
MDfeatures_clustering: attempt to cluster into variants with MD features by different methods.
Omicron: omicron results including MD results/Clustering map/structural view.
PublishData: data for publication.
Corre_clustering.png: correlation of MD features and variants clustering map without data selecting mutual residues in RMSD/Rg analysis.
Corre_clustering_wMutual_*.png: correlation of MD features and variants clustering map with data selecting mutual residues in RMSD/Rg analysis (* is the version number).
DistDistribution_all.png: distribution of distances of hydrogen bonds (overall/focus on certain range) without omicron result.
HBnum_all.png: the number of hydrogen bonds over time (6m0j/7a91/ground truth) without omicron result.
RMSD_Rg_HBac.png: results of RMSD/Rg/autocorrelation of hydrogen bonds without data selecting mutual residues in RMSD/Rg analysis.
RMSD_Rg_HBac_mutual.png: results of RMSD/Rg/autocorrelation of hydrogen bonds with data selecting mutual residues in RMSD/Rg analysis.
Reuters_graphics_20211123_anno.png: public heatlh plots from Reuters with manual annotation of variant shifts.
VariantVaccPlot_freq_****_anno.png: variant frequency plots (with public health data from CoVariants and Our World in Data) with manual annotation of variant shifts (**** is the date of plotting).
VariantVaccPlot_freq_1228_anno_filterBias.png: variant frequency plots (with public health data from CoVariants and Our World in Data) with manual annotation of variant shifts (**** is the date of plotting); filtering the bias in Israel case.
`delta_structural_chord_v*.png: structural view and chord plot for the results of the delta variant (* is the version number).
Reuters: raw public heatlh plots from Reuters.
StructuralView: raw data of strucutral views of the results of the delta variant.
VariantFrequency: raw variant frequency plots with public health data from CoVariants and Our World in Data.

Variants in this study

WHO label	PANGO lineage	PDB
Wild type	-	6m0j, 7a91
Omicron	BA.1	6m0j+schrodinger, 7a91+schrodinger
Omicron	BA.2	6m0j+schrodinger, 7a91+schrodinger
Omicron	BA.2.12.1	6m0j+schrodinger, 7a91+schrodinger
Omicron	BA.4&5	6m0j+schrodinger, 7a91+schrodinger
Alpha	B.1.1.7	6m0j+schrodinger, 7a91+schrodinger, 7mjn
Beta	B.1.351	6m0j+schrodinger, 7a91+schrodinger, 7v80
Gamma	P.1	6m0j+schrodinger, 7a91+schrodinger, 7v84
Delta	B.1.617.2	6m0j+schrodinger, 7a91+schrodinger, 7v8b
Delta Plus	AY.1	6m0j+schrodinger, 7a91+schrodinger
Epsilon	B.1.427/9	6m0j+schrodinger, 7a91+schrodinger
Lambda	C.37	6m0j+schrodinger, 7a91+schrodinger
Mu	B.1.621	6m0j+schrodinger, 7a91+schrodinger
Mu -R346K	-	6m0j+schrodinger, 7a91+schrodinger

6m0j: S1RBD:333-526; hACE2:19-615
7a91: S1RBD:323-555; hACE2:19-133,141-613
7mjn, 7v80, 7v84, 7v8b: S1RBD:331-530; hACE2:19-614

yuyuan871111/COVID19_Proj_toGitHub