Sculpting protein conformations

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Sometimes it is instructive to change the conformation of a protein model. Typically this means "sculpting" an experimentally-determined (empirical) model into a hypothetical conformation with some functional significance[1]. Here are described software packages that enable this to be done manually, using the mouse to drag portions of the original model into desired conformations.

As you sculpt a protein model, you are morphing it into a new conformation in real time. However, molecular morphing usually means saving a movie or animation that shows interpolated transitioning between two earlier-saved conformations, which may be empirical or theoretical. There are many examples of molecular morphs in Proteopedia. Slides explaining how to morph a sculpted protein are available at tinyurl.com/sculpting-proteins.


Contents

Samson

The free, open-source program Samson is available from samson-connect.net and in February 2020 is under active development by OneAngstrom.Com: see What's New in Samson 2020?. Samson has an extension application named Twister that enables dragging portions of a protein into new conformations with the mouse. Real-time minimization occurs while dragging, following the as-rigid-as-possible interpolation path[2][3]. You can click on atoms to set anchor points (shown as gold balls) that remain fixed during dragging. A video showing how to do this, step by step, is available at tinyurl.com/sculpting-proteins.

Twister alone does not prevent atomic clashes, but they can be avoided by turning on Minimize, which applies a universal force field. This is demonstrated in the movie available at tinyurl.com/sculpting-proteins. Samson can also create simulations that use any of a number of force fields provided, such as GROMACS (not illustrated here -- see Simulating small molecules and proteins).

Pros
  • Anchor points can be set that remain fixed during sculpting.
  • Minimization occurs in real time during dragging.
  • Activating Minimize avoids clashes and maintains correct geometry.
  • Interpolation methods are published[2][1][3].
  • Free software.

Cons

Sculpting 1AL1 with Twister in Samson (screen capture}. An anchor point (gold ball) was set at left before the movie starts. Mid-way, an anchor point was set in the middle of the polypeptide. Higher resolution version. Minimize was not turned on in this movie.

PyMOL

PyMOL, originally developed by Warren DeLano, is now maintained and licensed by Schrödinger. It includes a sculpting mode. A video showing how to do this, step by step, is available at tinyurl.com/sculpting-proteins.

Pros
  • Atomic clashes are avoided.
  • Minimization occurs in real time during dragging.

Cons

  • Sculpting in PyMOL is described as unsupported (see below) and there is no detailed documentation. However see the step-by-step instructional movie at tinyurl.com/sculpting-proteins.
  • PyMOL is not free, although many institutions have site licenses, and you may be able to obtain a free version for educational uses.

Sculpting 1AL1 with PyMOL (screen capture}. A video showing how to do this, step by step, is available at tinyurl.com/sculpting-proteins.

Sculpt (defunct)

Sculpt[4] is no longer available. It was initially released in 1994 by Mark Surles, Jane Richardson, David Richardson, and Frederick P. Brooks, Jr., and is described with the theoretical structure 1ssr. Formerly it was available as a stand-alone program, and also it was built-into Chime. A simulation of inhibitor binding to HIV protease that was created with Sculpt can be viewed at Molecular Playground/HIV Protease Inhibitor. A simulation of water molecules coalescing into a nano-droplet was done with Sculpt, and can be found at MolviZ.Org or by going directly to Water at BioModel.

Related Resources

References

  1. ↑ 1.0 1.1 Nguyen MK, Jaillet L, Redon S. ART-RRT: As-Rigid-As-Possible search for protein conformational transition paths. J Comput Aided Mol Des. 2019 Aug;33(8):705-727. doi: 10.1007/s10822-019-00216-w. , Epub 2019 Aug 21. PMID:31435895 doi:http://dx.doi.org/10.1007/s10822-019-00216-w
  2. ↑ 2.0 2.1 Nguyen MK, Jaillet L, Redon S. As-Rigid-As-Possible molecular interpolation paths. J Comput Aided Mol Des. 2017 Apr;31(4):403-417. doi: 10.1007/s10822-017-0012-y., Epub 2017 Mar 20. PMID:28321532 doi:http://dx.doi.org/10.1007/s10822-017-0012-y
  3. ↑ 3.0 3.1 Nguyen MK, Jaillet L, Redon S. Generating conformational transition paths with low potential-energy barriers for proteins. J Comput Aided Mol Des. 2018 Aug;32(8):853-867. doi: 10.1007/s10822-018-0137-7., Epub 2018 Aug 1. PMID:30069648 doi:http://dx.doi.org/10.1007/s10822-018-0137-7
  4. ↑ 4.0 4.1 Surles MC, Richardson JS, Richardson DC, Brooks FP Jr. Sculpting proteins interactively: continual energy minimization embedded in a graphical modeling system. Protein Sci. 1994 Feb;3(2):198-210. PMID:8003957

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Eric Martz

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