2. Feature Roadmap

The completed code will contain the following features:

  • Simulation of proteins protonation states
  • Support for small molecule protonation states, and tautomers through Epik calculations.
  • Support for implicit and explicit solvent models.
  • Support for instantaneous Monte Carlo, and Non-equilibrium (NCMC) state switches.
  • Compatibility with the Yank free energy calculation framework.

2.1. Development notes

This code is currently under heavy development. At the current time, we are ironing out potential bugs, and extending the test suite. Here is a status update on some of the features we’re working on.

2.1.1. Protein simulation

Our code is capable of performing instantaneous state switching for implicit solvent simulations. At the moment, we only support updating the protonation states of the sidechains if the following amino acids:

  • Glutamic acid, (pKa=4.4)
  • Aspartic acid, (pKa=4.0)
  • Histidine, (pKa delta=6.5, pKa epsilon = 7.1)
  • Tyrosine, (pKa=9.6)
  • Cysteine, (pKa=8.5)
  • Lysine, (pKa=10.4)

The pKa values used originate from [Mongan2004].

2.1.2. Small molecule support

Small molecule support is is a much anticipated feature that we plan to implement soon. The code will be extended to use output from Epik calculations ([Shelley2007], [Greenwood2010], [Epik2016]) to provide us with the populations of different protonation states and tautomers in aqueous solvent conditions. For parameter generation, we will rely on the GAFF forcefield [Wang2004], as provided with the antechamber program [Amber2016].

2.1.3. Explicit solvent

Explicit solvent is supported by the code, but it is not feature complete. The current version of the software only features a working implementation of instantaneous Monte Carlo. This will likely lead to low acceptance rates for protonation state switching. We are in the process of developing an approach that uses NCMC [Nilmeier2011], [Chen2015] but the implementation is not finished.