SEEKR2: Multiscale Milestoning Calculations of Kinetics and Thermodynamics
- Release:
2.1.4-beta
- Date:
Feb 02, 2024
SEEKR2 Simulation Enabled Estimation of Kinetic Rates version 2 is a package to perform simulations at multiple scales for the calculation of kinetics and thermodynamics quantities.
Most typically, one would use this package to obtain the kinetics and thermodynamics of binding and unbinding between a small molecule and biomolecular receptor. Also typically, this package performs molecular dynamics (MD) and Brownian dynamics (BD) simulations of the binding process within multiple regions of phase space, utilizing expensive, but highly accurate MD for regions where close molecular interaction would require high accuracy, but utilizing faster, but more approximate BD for regions of greater intermolecular distance. This way the advantages of each simulation regime is augmented and their disadvantages are reduced. The regimes are then combined using the theory of milestoning such that the kinetics and thermodynamics of the process under interest is obtained.
Two versions of milestoning theory are available to use in SEEKR2:
Markovian milestoning with Voronoi Tesselations (MMVT): Vanden-Eijnden, E.; Venturoli, M. Markovian Milestoning with Voronoi Tessellations. J. Chem. Phys. 2009, 130 (19), 194101. https://doi.org/10.1063/1.3129843
The original formulation of milestoning theory (Elber milestoning): Faradjian, A. K.; Elber, R. Computing Time Scales from Reaction Coordinates by Milestoning. J. Chem. Phys. 2004, 120 (23), 10880–10889. https://doi.org/10.1063/1.1738640
Cite SEEKR2
If you wish to cite SEEKR2, please cite the following paper:
Votapka, L. W.; Stokely, A. M.; Ojha, A. A.; Amaro, R. E. SEEKR2: Versatile Multiscale Milestoning Utilizing the OpenMM Molecular Dynamics Engine. J. Chem. Inf. Mod. 2022 62 (13), 3253-3262. DOI: 10.1021/acs.jcim.2c00501
You may also optionally cite one or more of the following papers:
Votapka, L. W.; Jagger, B. R.; Heyneman, A. L.; Amaro, R. E. SEEKR: Simulation Enabled Estimation of Kinetic Rates, A Computational Tool to Estimate Molecular Kinetics and Its Application to Trypsin–Benzamidine Binding. J. Phys. Chem. B 2017, 121 (15), 3597–3606. https://doi.org/10.1021/acs.jpcb.6b09388.
Jagger, B. R.; Ojha, A. A.; Amaro, R. E. Predicting Ligand Binding Kinetics Using a Markovian Milestoning with Voronoi Tessellations Multiscale Approach. J. Chem. Theory Comput. 2020. https://doi.org/10.1021/acs.jctc.0c00495.
Jagger, B. R.; Lee, C. T.; Amaro, R. E. Quantitative Ranking of Ligand Binding Kinetics with a Multiscale Milestoning Simulation Approach. J. Phys. Chem. Lett. 2018, 9 (17), 4941–4948. https://doi.org/10.1021/acs.jpclett.8b02047.
Votapka LW, Amaro RE (2015) Multiscale Estimation of Binding Kinetics Using Brownian Dynamics, Molecular Dynamics and Milestoning. PLOS Computational Biology 11(10): e1004381. https://doi.org/10.1371/journal.pcbi.1004381
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