Enlighten2: molecular dynamics simulations of protein–ligand systems made accessible

Abstract

Motivation Experimental structural data can allow detailed insight into protein structure and protein-ligand interactions, which is crucial for many areas of bioscience, including drug design and enzyme engineering. Typically, however, little more than a static picture of protein-ligand interactions is obtained, whereas dynamical information is often required for deeper understanding and to assess the effect of mutations. Molecular dynamics (MD) simulations can provide such information, but setting up and running these simulations is not straightforward and requires expert knowledge. There is thus a need for a tool that makes protein-ligand simulation easily accessible to non-expert users. Results We present Enlighten2: efficient simulation protocols for protein-ligand systems alongside a user-friendly plugin to the popular visualization program PyMOL. With Enlighten2, non-expert users can straightforwardly run and visualize MD simulations on protein-ligand models of interest. There is no need to learn new programs and all underlying tools are free and open source. Availability The Enlighten2 Python package and PyMOL plugin are free to use under the GPL3.0 licence and can be found at https://enlighten2.github.io. We also provide a lightweight Docker image via DockerHub that includes Enlighten2 with all the required utilities.

The Role of Cytochrome P450 AbyV in the Final Stages of Abyssomicin C Biosynthesis

“…[25] To explore the likely enzyme-substrate interactions of both atropisomers of spirocycle 3, we used molecular docking to obtain initial positions of 3 near the heme group in chain A of the AbyV crystal structure. We then performed multiple short molecular dynamics simulations for both atropisomers with heme modelled in its compound I state (10 × 200 ps runs for each, using the Enlighten protocols, [26] details in the Supporting Information, Figure 3C). Based on the final half of the simulations and the reactivity criteria for epoxidation proposed by Lonsdale, Harvey and Mulholland (Compound I oxygen to epoxidised C distance < 4 Å, compound I heme iron, oxygen, epoxidised C angle between 110 and 140°), [27] a higher percentage of reactive poses was observed for one atropisomer of the substrate (81 % vs. 42 %).…”

A novel thymidine phosphorylase to synthesize (halogenated) anticancer and antiviral nucleoside drugs in continuous flow

“…To perform the molecular dynamics studies, the Enlighten2 plugin for PyMOL was used. 43 Simulations were performed with the monomeric structure of HeTP and with mobility only on the residues at 12 Å surrounding the docked substrate. After minimization of the system, the MD simulation was performed for 1 ns.…”

Boosting the Full Potential of PyMOL with Structural Biology Plugins

“…Many environments for MD are available; however, the setup of programs for MD still requires detailed knowledge in the field. Enlighten2 [ 97 ], an easy-to-install interface to the Amber force-field [ 98 ], provides direct access to MD simulations. Protocols to set up MD simulations, which have already been tested and used in the previous version of Enlighten [ 99 , 100 , 101 , 102 ], together with the GUI, make MD accessible to all.…”