Molecular Dynamics (MD) Simulations

FEP-Guided Synthesis Prioritization

Key Features:

• Alchemical Free Energy Perturbation (FEP/TI) — GROMACS/AMBER GPU-accelerated relative binding affinity calculations predicting ΔΔG within ~1 kcal/mol of experimental SPR/ITC data for well-calibrated targets.
• MM/PBSA End-Point Scoring — Post-trajectory free energy decomposition into enthalpic and entropic contributions, identifying whether affinity gains are driven by H-bond networks or hydrophobic burial.
• Selectivity Profiling — FEP calculations across homolog panels (kinase family, GPCR subtypes) flag off-target risks before synthesis commitment.

What We Offer: For lead optimization programs, FEP replaces intuition with thermodynamic certainty — you synthesize only modifications with predicted affinity improvements. For biotechs without alchemical calculation infrastructure, we deliver ΔΔG rankings with biophysical validation to confirm directionality.

Microsecond Trajectories for Drug-Design-Ready Insights

Key Features:

• Explicit-Solvent Microsecond Sampling — GROMACS/AMBER/NAMD with AMBER ff19SB or CHARMM36m force fields; particle-mesh Ewald electrostatics; reproducible trajectory protocols.
• Induced-Fit and Cryptic Pocket Discovery — Trajectory analysis reveals transient pocket openings and loop rearrangements invisible in crystal structures, updating docking and virtual screening protocols.
• Ligand-Binding Stability Assessment — Docking poses are equilibrated in explicit solvent to test whether predicted binding modes survive thermal fluctuations and solvent competition.

What We Offer: For seed-stage biotechs, dynamic validation of docking poses before spending on synthesis. For pharma, conformational ensemble data that supports regulatory filings and intellectual property claims around novel binding modes.

Capturing Lipid-Driven Biology

Key Features:

• Explicit Lipid Bilayer Assembly — Automated bilayer construction (POPC, POPE, cholesterol mixtures) with protein orientation guided by Cryo-EM density or OPM database; hydration and ionic strength matched to experimental conditions.
• Gating and Allosteric Coupling — Microsecond trajectories reveal lipid-mediated conformational transitions, sodium/proton coupling pathways, and allosteric signal propagation in GPCRs, ion channels, and transporters.
• Ligand Entry and Membrane Partitioning — Enhanced sampling (steered MD, metadynamics) maps ligand entry pathways from bulk solvent through the bilayer to the orthosteric site.

What We Offer: For membrane protein programs where crystallization fails and Cryo-EM provides only a few states, MD reveals the dynamic landscape connecting those states — critical for understanding activation mechanisms and designing state-selective modulators.

Dynamic Models for Non-Traditional Targets

Key Features:

• DNA/RNA Flexibility and Bending — Explicit-solvent trajectories capturing major/minor groove width fluctuations, base-pair opening events, and backbone conformational transitions.
• Protein-Nucleic Acid Interaction Dynamics — Simulation of transcription factor binding, CRISPR R-loop formation, and helicase translocation along nucleic acid substrates.
• Groove Binding and Intercalation Analysis — Trajectory-derived binding free energy profiles for small molecules targeting DNA/RNA grooves, including sequence-specific selectivity.

What We Offer: For nucleic acid-targeting programs where static structures provide incomplete pictures of ligand accessibility, MD reveals transient groove conformations and competitive ion effects that determine binding selectivity.

Accessing Millisecond Events on Microsecond Budgets

Key Features:

• Parallel Temperature Replicas — Multiple simultaneous simulations at different temperatures exchange conformations, accelerating escape from kinetic traps and sampling rare states.
• Free Energy Landscape Mapping — Cluster analysis and principal component analysis of REMD trajectories reveal low-energy conformational basins and transition pathways.
• Rare Event Access — Cryptic pocket opening, loop folding, and allosteric switching events that standard MD cannot reach within accessible timescales.

What We Offer: For targets with known inactive and active states but unclear transition mechanisms, REMD provides thermodynamic and kinetic landscapes that guide the design of state-selective allosteric modulators and covalent traps.

Millisecond-Scale Assembly and Membrane Remodeling

Key Features:

• Martini Force-Field Large Assemblies — Protein complexes, viral envelopes, and lipid nanoparticles simulated at ~1000× speedup over all-atom, accessing biologically relevant timescales.
• Membrane Remodeling and Fusion — Bilayer curvature, pore formation, and vesicle fusion events relevant to drug delivery and membrane protein biogenesis.
• Protein-Protein Association Kinetics — CG simulations predict encounter rates and complex lifetimes for PPI targets too large for all-atom approaches.

What We Offer: For large-scale systems where all-atom MD is computationally prohibitive, CG provides morphological and kinetic insights at experimental timescales, validated against Cryo-ET and light-sheet microscopy.