Models and Methodologies

Atomic Resolution Brownian Dynamics

Download the latest release of ARBD

Complementing experimental investigations, computational approaches yield a molecular picture of processes that are too small and fast to resolve experimentally in biological and nanotechnological systems. The most widely employed biological simulation method, all-atom MD, describes molecules with atomic resolution. However, MD is computationally expensive and might be overkill for many tasks. Coarse-graind (CG) Brownian dynamics (BD) simulations are a promising alternative for modeling macromolecular complexes.

BD achieves computational economy while keeping molecular-level detail by modeling the solute through point-like particles with parameterized properties but treating solvent molecules implicitly. Hence, CG BD simulations can be used to overcome the constraints of all-atom MD simulations, which are typically limited by computational resources to time and length scales under about 10 microseconds and 30 nanometers.

Atomic Resolution Brownian Dynamics (ARBD) is a code that takes advantage of GPUs to facilitate fast simulations. Uniquely, ARBD supports models that contain both point-like particles and grid-specified physical particles that possess both position and orientation.

You can download ARBD, compile with a recent version of the CUDA toolkit and begin testing included examples. Please contact Chris Maffeo at cmaffeo2@illinois.edu if you have any trouble using the software. Also, please note that the software is currently offered as an alpha release.

CUFIX: Non-bonded Fix (NBFIX) parameters for the CHARMM and AMBER force fields

Over the past decades, molecular dynamics (MD) simulations of biomolecules have become a mainstream biophysics technique. As the length and time scales amenable to the MD method increase, shortcomings of the empirical force fields—which were developed and validated using relatively short simulations of small molecules—become apparent. One common artifact is artificial aggregation of water-soluble biomolecules, which has been observed in a variety of systems, including electrolyte solutions, intrinsically disordered proteins, lipid bilayer membranes and DNA arrays. Here, we report a systematic refinement of Lennard-Jones parameters (CUFIX) describing amine-carboxyate, amine-phosphate, and aliphatic carbon-carbon interactions, which brings the results of MD simulations of proteins, nucleic acids, and lipids in remarkable agreement with experiments. To refine the amine-carboxylate and aliphatic carbon-carbon interactions, we matched the simulated osmotic pressure of amino acid solutions to the experimental data. Similarly, we refined the amine-phosphate interaction by matching the simulated and experimental osmotic pressure of a DNA array. We demonstrate the utility of our CUFIX corrections through simulations of lysine-mediated DNA—DNA forces, lipid-bilayer membranes and folded proteins. As our refinement neither affects the existing parameterization of bonded interaction nor does it alter the solvation free energies, it improves realism of an MD simulation without introducing any new artifacts.

How to use CUFIX:

  • AMBER ff99 variants in the Gromacs format:
    • > Option 1: If you want to use a complete package that was used for our publications, download ff99sb-ildn-phi-bsc0-cufix. Make sure our CUFIX corrections are optimized with the TIP3P water model (use tip3p.itp).
    • > Option 2: If you want to integrate CUFIX to your version of AMBER ff99 variants, follow these steps.
      • >> Download ff99sb-ildn-phi-bsc0-cufix package.
      • >> Copy the following files in the downloaded package to your gromacs-format ff99 folder: cufix.itp, mg-sol6.itp mg-sol6.pdb ca-sol7.itp ca-sol7.pdb.
      • >> Replace atom types of O1P and O2P atoms (O2) with ON2 for all nucleotides in dna.rtp and rna.rtp. ON2 atom type is defined in cufix.itp.
      • >> Add #include "cufix.itp" to forcefield.itp between #include "ffnonbonded.itp" and #include "ffbonded.it".
      • >> Delete the following ions from ffnonbonded.itp: Li, Na, K, Cl, MG, Rb, Cs, F, Br, I. CUFIX uses new ion parameters by the Cheatham group.
      • >> You're ready to go! Make sure that CUFIX is optimized with tip3p.itp.
  • ​AMBER ff99 variants in AMBER format
    • > Download frcmod.ff99cufix.
    • > This frcmod file will work with any ff99 variant protein force field in combination with leaprc.water.tip3p. frcmod files for nucleic acids and lipid are coming soon.
    • For example, do the followings in the leap command:
      • source <A FF99 PROTEIN FORCE FIELD CMD FILE>
        source leaprc.water.tip3p
        cufix = loadamberparams frcmod.ff99cufix
  • CHARMM 36/27/22 force fields
    • > Download CHARMM36/27/22 force fields: stream file for CHARMM and NAMD packages
    • > Replace the standard toppar_water_ions.str with the downloaded file.
    • > Our CUFIX corrections are optimized for CHARMM36-version ion parameters (LIT, SOD, K, MG, CAL and CL) with CHARMM-format TIP3P water model.
    • > For magnesium and calcium ions, we use hexa- or hepta-hydrated forms, respectively. The downloaded file contains RESI definitions for these Mg/Ca-water complexes, but additional bonds (extrabonds) are required between Mg/Ca and water oxygen atoms. Please refer to our DNA origami tutorial to learn how to use it.
  • Anton

 

Coarse-Grained DNA model

A simple coarse-grained model of single-stranded DNA (ssDNA) was developed, featuring only two sites per nucleotide that represent the centers of mass of the backbone and sugar/base groups. Interactions between sites are described using tabulated bonded potentials optimized to reproduce the solution structure of DNA observed in atomistic molecular dynamics simulations. Isotropic potentials describe nonbonded interactions, implicitly taking into account the solvent conditions to match the experimentally determined radius of gyration of ssDNA. The model reproduces experimentally measured force–extension dependence of an unstructured DNA strand across 2 orders of magnitude of the applied force. A complete description of the model was published in the Journal of Chemical Theory and Computation.

All required configuration files can be downloaded. To use the model, a custom version of NAMD must be compiled using a patch provided in the archive. For questions, contact Christopher Maffeo.

Grid-steered molecular dynamics

Grid-steered molecular dynamics (G-SMD) is a flexible method for applying forces that our group has implemented in NAMD. Much as in experiment, simulation studies often involve perturbing the system in some way and monitoring the result. As simulations have become bigger, longer, and more complex, the need for more sophisticated forcing techniques has increased. In the G-SMD method, an arbitrary external potential field, defined on a grid, is applied to desired target atoms with arbitrary coupling, making it a very flexible tool. Because it is coded natively in NAMD, the performance impact of G-SMD is minimal. G-SMD provides tremendous flexibility in the forces that can be applied. It was originally designed to apply an enhanced electrostatic field to DNA threaded through the membrane protein α-hemolysin in order to realistically increase the DNA translocation speed. It is the basis for a method of combining crystallographic structures and cryo-EM maps to obtain an all-atom model developed by Trabuco et al. and called Molecular Dynamics Flexible Fitting (MDFF). A variation of this approach was also recently used by our group to study the mechanical properties of a complete microtubule.