CHARMM-GUI 10 years for biomolecular modeling and simulation

Abstract

CHARMM-GUI, http://www.charmm-gui.org, is a web-based graphical user interface that prepares complex biomolecular systems for molecular simulations. CHARMM-GUI creates input files for a number of programs including CHARMM, NAMD, GROMACS, AMBER, GENESIS, LAMMPS, Desmond, OpenMM, and CHARMM/OpenMM. Since its original development in 2006, CHARMM-GUI has been widely adopted for various purposes and now contains a number of different modules designed to set up a broad range of simulations: (1) PDB Reader & Manipulator, Glycan Reader, and Ligand Reader & Modeler for reading and modifying molecules; (2) Quick MD Simulator, Membrane Builder, Nanodisc Builder, HMMM Builder, Monolayer Builder, Micelle Builder, and Hex Phase Builder for building all-atom simulation systems in various environments; (3) PACE CG Builder and Martini Maker for building coarse-grained simulation systems; (4) DEER Facilitator and MDFF/xMDFF Utilizer for experimentally guided simulations; (5) Implicit Solvent Modeler, PBEQ-Solver, and GCMC/BD Ion Simulator for implicit solvent related calculations; (6) Ligand Binder for ligand solvation and binding free energy simulations; and (7) Drude Prepper for preparation of simulations with the CHARMM Drude polarizable force field. Recently, new modules have been integrated into CHARMM-GUI, such as Glycolipid Modeler for generation of various glycolipid structures, and LPS Modeler for generation of lipopolysaccharide structures from various Gram-negative bacteria. These new features together with existing modules are expected to facilitate advanced molecular modeling and simulation thereby leading to an improved understanding of the structure and dynamics of complex biomolecular systems. Here, we briefly review these capabilities and discuss potential future directions in the CHARMM-GUI development project. © 2016 Wiley Periodicals, Inc.

Keywords: Coarse-grained simulation; Glycan; Membranes; Protein-ligand interactions; mmCIF.

Figure 1

Schematic view of modules in CHARMM-GUI Input Generator.

Figure 2

Molecular graphics views of (A) KIX domain and co-activator KID (PDB:1KDX), (B) DOX-P reductoisomerase with NADH (PDB:4ZQG), (C) lipid-like pseudo atom packing around multidrug transporter EmrD (PDB:2GFP) with the primary system indicated by lines, and (D) after replacement of lipid-like pseudo atoms in (C) with corresponding all-atom lipids (before equilibration), (E) electrostatic potential on the solvent-accessible surface representation of KIX domain, and (F) iso-electrostatic potential contour of KIX domain.

Figure 3

Molecular graphics views of (A) bilayer, (B) nanodisc, (C) monolayer, (D), micelle, (E) inverse hexagonal lipid phase, and (F) vesicle. The mechanosensitive channel of large conductance (MscL) is embedded in a bilayer, a micelle, and a vesicle. Water molecules are shown as blue spheres only in (C), (E), and (F). The alkane molecules in the hexagonal phase system are shown as red spheres.

Figure 4

Conversion of (A) a Martini bilayer system to (B) an all-atom system. The mechanosensitive channel MscL protein is embedded in a POPC bilayer. Water molecules and ions are not shown for clarity. Different subunits of the MscL are drawn with different colors.

Figure 5

Structure of glycoconjugates: BDDM for dodecyl-beta-D-maltoside, GM1 for monosialotetrahexosyl ganglioside, PrP^C for a glycosylphospatidylinositol (GPI)-anchored human prion protein (cyan) with two N-glycans (green) [94], and Ec.R1.O6 for E. coli lipopolysaccharide (LPS) with R1 core (blue for the inner core and yellow for the outer core) and two repeating units of O6 antigen (cyan) [95].

Figure 6

Illustration of carbohydrate annotation procedure in Glycan Reader. (A) Molecular topology is built using HETATM and CONECT records in a PDB file. (B) Potential carbohydrate molecules are examined for anomeric carbon, stereochemistry of each ring carbon atoms, and exocyclic groups. (C) Carbohydrate type is annotated. (D) Glycosidic linkages are assigned between monosaccharides. Figure reproduced with permission from Journal of Computational Chemistry [93].

Figure 7

reMD simulation of lysozyme in solution. Multiple spin labels are added to one protein residue with the nitroxide groups shown as red spheres. The protein is shown as orange ribbon. The backbone atoms of the restrained residues are shown in blue spheres. Water molecules are removed for clarity.