Published August 30, 2025 | Version v1

Polyamine-dependent metabolic shielding regulates alternative splicing

Description

Abbreviations:

SF3A3: Splicing Factor 3a Subunit 3

CK1: Casein kinase 1

PUT: Putrescine

SPD: Spermidine,

SPM: Spermine,

BENSpm: N1,N11-bis(ethyl)norspermine

 

Computational Data:

0-molecular_docking (best binding poses)

• SF3A3: binary complexes between Splicing Factor 3a Subunit 3 and the four polyamines (putrescine, spermidine,  spermine, N1,N11-bis(ethyl)norspermine). 10 best poses for each system in PDB format.

• SF3A3_CK1: ternary complexes between Splicing Factor 3a Subunit 3, Casein kinase 1 and the four polyamines (putrescine, spermidine,  spermine, N1,N11-bis(ethyl)norspermine). Best pose for each system in PDB format.

 

1-conventional_MD (molecular dynamics simulations)

• SF3A3: binary complexes between Splicing Factor 3a Subunit 3 and the four polyamines (putrescine, spermidine,  spermine, N1,N11-bis(ethyl)norspermine). 100 frames in PDB format collected from 10 independent simulations per system with frame frequency 1/10 ns.

-          salt_bridge_analysis: interatomic distances in Å between the nitrogen of each ammonium group for each polyamine, and the center of mass of the carboxylate oxygens of each Glu sidechain of the acidic surrounding the phosphorylatable serines.

• SF3A3_CK1: ternary complexes between Splicing Factor 3a Subunit 3, Casein kinase 1 and the four polyamines (putrescine, spermidine,  spermine, N1,N11-bis(ethyl)norspermine). 10 frames in PDB format collected from one simulation per system with frame frequency 1/10 ns.

 

2-REUS_MD: (Hamiltonian Replica Exchange Umbrella Sampling simulations)

• SF3A3_PUT: (Un)binding free energy profile of putrescine to SF3A3.

• SF3A3_SPD: (Un)binding free energy profile of spermidine to SF3A3.

• SF3A3_SPM: (Un)binding free energy profile of spermine to SF3A3.

• SF3A3_BENSpm: (Un)binding free energy profile of N1,N11-bis(ethyl)norspermine to SF3A3.

• peptide_SPD: (Un)binding free energy profile of spermidine to SF3A3 cognate peptide.

• peptide_SPM: (Un)binding free energy profile of spermine to SF3A3 cognate peptide.

Each folder contains the metadata file (meta) defining the simulation windows and biasing potential for each system, the raw data for each simulation window (clean_xx.dat) and an execution script for computing the potentials of mean force (PMF) with the Weighted Histogram Analysis Method as implemented in the WHAM program (run_wham.sh).

 

Files

0-molecular_docking.zip

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