Combining Two Techniques

Many theoretical approaches and simulation methods have been used to estimate both the thermodynamics and kinetics of binding. For instance, specialized machinery and long molecular dynamics (MD) simulations can be used in a ‘brute force’ approach, although it is relatively costly compared to other methods. At a length far from the binding site, Brownian dynamics (BD) can also be used to approach the problem of binding kinetics. With the molecular flexibility of MD and the efficiency of BD, SEEKR can affectively compute the kinetics and thermodynamics of most receptor-ligand systems.

This work comes from the following:

Welcome to SEEKR!

SEEKR is a collection of scripts and templates designed to automate the preparation and analysis of ligand-receptor kinetic calculations that use both MD and BD, and combine the results using the theory of milestoning.

Getting Started

How To Cite SEEKR

After using SEEKR, please cite both of the following papers:

Votapka LW, Jagger BR, Heyneman AL, Amaro RE (2017) 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. Just Accepted. doi:10.1021/acs.jpcb.6b09388

Votapka LW, Amaro RE (2015) Multiscale Estimation of Binding Kinetics Using Brownian Dynamics, Molecular Dynamics and Milestoning. PLoS Comput Biol 11(10): e1004381. doi:10.1371/journal.pcbi.1004381

SEEKR Programs in Three Categories

Title Brief Synopsis
1 Prepare SEEKR accepts input from the user in order to construct all the necessary files needed to run simulations. When run, the user will have all the required files arranged and poised for simulation and milestoning calculations.
2 Run SEEKR aids the user in running simulations locally and on supercomputers. For instance, SEEKR contains a script to prepare the submission to a SLURM supercomputer queue. Other scripts use previous BD trajectory output to prepare and run ensembles of BD simulations.
3 Analyze When all the simulations are complete, the user can run an analysis script that constructs the milestoning model, and performs all the milestoning and error calculations, providing the user with kinetic and thermodynamic information, including kon, koff, and the free energy profile.

Helpful Links

Outlined in the tutorial and the README, you will need each of the listed programs above downloaded and operational before you can utilize SEEKR. More…

Developers of SEEKR