SEEKR

SEEKR estimates multiscale molecular kinetic rates for binding, unbinding, and transport by combining molecular dynamics, Brownian dynamics, and milestoning theory to compute association and dissociation rate constants and binding free energies.

Key Features:

• Multiscale integration: Integrates molecular dynamics, Brownian dynamics, and milestoning to simulate molecular interactions across spatial and temporal scales.
• Molecular dynamics simulations: Simulates atomic-level interactions over time to capture detailed conformational dynamics.
• Brownian dynamics simulations: Models stochastic motion of particles in a fluid medium to capture diffusive approaches and long-range encounters.
• Milestoning-based rate computation: Uses milestoning theory to divide reaction pathways into discrete milestones and compute transition rates between them.
• Kinetic and thermodynamic parameter estimation: Estimates association rate constants (k_on), dissociation rate constants (k_off), and binding free energies (ΔG_bind).

Scientific Applications:

• Binding and unbinding kinetics estimation: Computes association and dissociation rates and binding free energies for molecular complexes.
• Noncovalent interaction studies (trypsin‑benzamidine): Applied to the trypsin‑benzamidine system yielding k_on = (2.1 ± 0.3) × 10^7 M^-1 s^-1, k_off = 83 ± 14 s^-1, and ΔG_bind = -7.4 ± 0.1 kcal·mol^-1 compared with experimental values of 2.9 × 10^7 M^-1 s^-1, 600 ± 300 s^-1, and -6.71 ± 0.05 kcal·mol^-1.
• Experimental validation: Enables direct comparison of computed kinetic parameters with experimental measurements to assess accuracy.

Methodology:

Computational methods explicitly include molecular dynamics, Brownian dynamics, and milestoning theory, with milestoning dividing reaction pathways into discrete milestones to compute transition rates.