IDH1 Research Platform

MD Simulations

EXPLORATORY

6 simulations · 52 GPU·h

Molecular Dynamics (MD) simulations model how proteins move, fold, and interact with drug molecules over time. Each simulation runs on GPU hardware using OpenMM, tracking every atom at femtosecond resolution.

▶How does MD simulation setup work?

Each row represents a protein (or protein-drug complex) simulated under physiological conditions: 310 K (body temperature), explicit water solvent (TIP3P), 150 mM NaCl, periodic boundary conditions. Simulation types include SMN oligomerization, hnRNP A1–ISS-N1 binding, risdiplam mechanism, NCALD calcium dynamics, PLS3 actin bundling, and SMN–Gemin2 stability.

Key metrics. RMSD— < 2 Å plateau = stable fold; increasing = unfolding. Binding energy— < −7 kcal/mol = strong drug binding. Contact persistence — percent of time the drug maintains key interactions.

DiffDock predicts a static binding pose; MD tests whether that pose is dynamically stable. A drug that stays bound for 100 ns is a much stronger candidate than one that dissociates after 10 ns. GPU hours estimate compute cost on a single NVIDIA A100.

Planned / Running Simulations

Simulation	Target	Type	PDB / AF2	Atoms	Time (ns)	GPU Hours	Force Field
SMN Protein Self-Oligomerization	SMN_PROTEIN	protein_protein	4QQ6	45,000	100	8	amber14-all.xml
hnRNP A1 binding to ISS-N1 RNA	SMN2	protein_rna	4YOE	35,000	50	4	amber14-all.xml
SMN2 pre-mRNA + Risdiplam binding	SMN2	protein_ligand	-	25,000	50	4	amber14-all.xml
Neurocalcin-delta Calcium Binding Dynamics	NCALD	protein_ligand	AF-Q6P2D0-F1	30,000	200	16	amber14-all.xml
Plastin-3 Actin Bundling Mechanism	PLS3	protein_protein	1AOA	80,000	100	12	amber14-all.xml
SMN-Gemin2 Complex Stability	SMN_PROTEIN	protein_protein	2LEH	50,000	100	8	amber14-all.xml

SMN Protein Self-Oligomerization

Simulate SMN Tudor domain self-association. SMN forms oligomers essential for Gems body formation and snRNP assembly. Understanding oligomerization dynamics reveals why reduced SMN (as in SMA) leads to functional collapse.

hnRNP A1 binding to ISS-N1 RNA

Simulate hnRNP A1 RRM domain binding to ISS-N1 (intron 7 +10 to +24). This is the interaction that nusinersen blocks. Understanding binding dynamics reveals small molecule disruption opportunities.

SMN2 pre-mRNA + Risdiplam binding

Simulate risdiplam (Evrysdi) binding to SMN2 pre-mRNA 5' splice site. Risdiplam stabilizes U1 snRNP binding, promoting exon 7 inclusion. Understanding the binding mode guides next-gen splicing modulator design.

Each simulation generates 3 Python scripts (setup, production, analysis). Run on GPU-equipped machines for best performance.