Introduction

BioAdviser for windows is a software application that brings high-quality, super-fast molecular rendering. Targeting the display, analysis and manipulation of large biological molecules including proteins and nucleic acids, it also deliverssuperb tools for analysis of smaller molecules.

The molecules can be viewed in Wire Frame, Ball and Stick, Cylinder and Space Filling modes. Protein specific features include representationby Lines, Wires, Flat and Solid Ribbons. Secondary structures can be viewed also using Tubes and Motifs. For Nucleic Acids the program offer BackBone, Rings and Ladder representations.

BioAdviser Fast Mode offers simplified molecular rendering that has only pixel and ball representation. However, using this mode the user open and manipulate structures that have hundreds of thousands of atoms using very moderate hardware.

BioAdviser implements multiple molecular manipulation tools, including tools for hiding, showing and focusing on sub-structures. The selection tools allow the user to perform operations on specific, selected subsystems of the entire structure.

The most important protein-specific molecular manipulation tools (like torsion or side-chain rotations) are also implemented. In addition to these tools, BioAdviser facilitates the initialization and analysis of the result of MOPAC 2002 jobs.

Visualization Capabilities

The molecules can be viewed in Wire Frame, Ball & Stick, Cylinder and Space Filling modes. In protein specific features program offers Lines, Wires, Flat and Solid Ribbons. Secondary structures can be viewed also using Tubes and Motifs. For Nucleic Acids the program offers Backbone, Rings and Ladder representation. Special Fast Mode offers simplified molecular rendering that has only pixel and ball representation. Using the fast mode the user can open and manipulate structures that have hundreds of thousands of atoms using very moderate hardware. Move your mouse over “More” to browse through specific descriptions.

Rendering of small molecules

BioAdviser offers excellent visualization tools for displaying the small and medium size molecules. It features wire-frame, ball and stick, cylinders and spheres representation of the molecular structures. The display can be further customized by the selection of sphere, balls and cylinder sizes. The lights can be added, deleted and moved. In addition to that, the selection facility allows to apply different view methods for different parts of the molecule.

Rendering of proteins

BioAdviser visualization tools for proteins are very rich. They offer the following modes and protein specific features:

Ca Wire - in this mode a single line joining C atoms is drawn. Wire Ribbon (Line) - a ribbon created by wireframe-like lines is drawn along peptide bonds. Flat Ribbon - flat, sheet-like ribbon is drawn along peptide bonds. Solid Ribbon - a ribbon is formed as a filled thick shape with varying size and color. Tubby - a kind of tube is drawn along peptide bonds.
Motifs - the schematic 3D objects are drawn to represent the tertiary structure of proteins: cylinders for helices, flat ribbons with arrows for beta-sheet segments and tubes for random-coil section

Rendering of DNA/RNA molecules

BioAdviser visualization tools for proteins are also rich. They offer the following modes and DNA specific features:

• Backbone - shows DNA/RNA backbone using a solid ribbon
• Rings - adds hexagonal “rings” that represent the bases
• Ladder - shows the backbone and simplified bases representations as “ladder rungs”

Rendering of very large structures One of unusual features of BioAdviser is its Fast Mode. Specially optimized with rendering speed and memory requirements in mind, the Fast Mode offers the ability to interactively manipulate structures with several hundreds thousands and millions of atoms. This ability comes at a price of two simple, yet sufficient, super-fast modes: Pixel - every atom is represented by a pixel in 3D space Ball - every atom is represented by a bitmap representation of a varying size ball.

BioAdviser implements very reach set of tools for visual manipulation of the molecular structures. Some of them are innovative BioAdviser specific tools. In addition to their innovative features, they were designed to enhance manipulation of the very large molecular structures.

View transformation tools facilitates the modification of the view position of the viewer against the molecular system and for modifying some viewing parameters to enhance the molecule visual perception.

• BA manipulator
  This innovative tool facilitates the application of the most of important geometrical transformations using mouse movement and buttons without switching the tool. This tool can be used to manipulate as many as possible degrees of freedom of the viewer. The tool performs the following operations:
• Rotate “out-of-plane” - mouse movement with left mouse button down, this tool facilitates out-of-plane rotations of the molecular system
• Rotate “in-plane” - horizontal mouse movement with right mouse button down, this tool facilitates in-plane rotations of the molecular system
• Zoom - vertical mouse movement with right mouse button down, this tool facilitates the zoom of the molecular system (Move of the observer in the direction perpendicular to the screen)
• Move - mouse movement with both mouse buttons down together, this tool facilitates 2D movement (in-plane) of the molecular system
• Spherical Zoom-In
  This tool facilitates fast zoom-in into a spherical region of variable size around an atom. Using the tool user can point an atom by clicking on it and drag the mouse with the left button down. The 3D sphere is drawn in the system with the radius controlled by the mouse movement. The radius value is displayed on the status bar. When the mouse button is released the atoms inside the sphere fit into the view window with the initial atom centered in the window. This command makes all atoms that fall into the sphere visible and all that are outside - invisible. The previous visibility of an atom is ignored. The atoms that fall into the sphere are visible. The atoms outside the sphere are hidden.
• Rectangular Zoom-In
  This tool facilitates fast zoom-in into a rectangular region of variable size on the current 3D view. Using the tool the user can draw a rectangle with the mouse left button down. The rectangle is drawn with size and shape controlled by the mouse movement. When the mouse button is released the atoms that fall into the rectangle fit into the current view. This command makes all atoms that fall into the rectangle visible and all that are outside - invisible. The previous visibility of an atom is ignored. The atoms that fall into the rectangle are visible. The atoms outside the rectangle are hidden.
• Show All
  This tool restores visibility for all atoms that may happen to be hidden as a result of other commands and tools.
• Clipping Spheres and Planes
  This tool facilitates the accurate establishment for clipping regions: spherical and rectangular. For detailed instruction go to the tool description.
• Animations
  BioAdviser for Windows implements the animation toolbar that facilitates the animated presentation of molecular systems on the screen.

BioAdviser strict conformance to document-view model allowed for the definition of the other than 3D structure view types. These view types allow for analysis for some other global properties of biological molecules, particularly, proteins.

• Amino Acid sequence view type allows for analysis of protein primary structure using variety of visual representations
• Properties plot draw curves of the variation of important residue properties against the amino-acid sequence
• Ramachandran plot displays statistics of secondary structure angles
• PDB Edit view type allows for inspection and modification of the PDB text file representation of the structure

BioAdviser for Windows facilitates the modification of molecules it displays. The current set of available operations include:

• Copying and pasting parts of molecular system
• Adding hydrogen atoms to fill the valence of the system
• Move molecules in space
• Rotate side chains and change T-angle (torsion angle)
• Mutate aminoacids Build protein from aminoacids
• Change bond type
• Delete atom

Using PDB Edit view type the molecular system can be edited through its text representation.

Analysis features

In addition to visualization and modeling features BioAdviser implements some very important analysis tools like Compare function, designed for comparisons between conformations of protein chains, Measure facility, that allows for different measurements between atoms of the Molecular structure and Properties Plots that can analyze the structure-activity relations along protein chains. As the special feature, BioAdviser can use MOPAC 2002 semi-empirical program (not included in the basic product package) to compute charges and variety of electronic properties of molecules.

Protein analysis

Common structure comparison

BioAdviser for Windows offers the tool necessary to superimpose two selected sections of peptide chains according to RMS criterion. Using this tool the user can create a new system where two peptide chains (target and probe) are superimposed by the requirement that RMS of distances between respective Calpha atoms is minimized.

Using the probe and target documents this command starts comparison computation. BioAdviser starts to compute the new orientation of probe against target such that the RMS of the distance between CA atoms in selected residues is minimized. The optimization is visualized by the creation of the special molecular document in which the CA atoms of both initial systems are displayed. When the optimizations ends, BioAdviser displays the numerical information about optimization. At the end of calculations BioAdviser creates the new document (called SystemSystem) that contains the probe and target superimposed.

Distances

Measuring atom-atom distance

BioAdviser for Windows offers two measurement tools: Atom-Atom pair and mulitlateral. Using these tools the user can measure distances between atoms. The results are displayed on the screen with colored lines representing the distance and/or in “Distances” Edit box from where the data can be transfered to another program. The distance box monitors the atom-atom distances computed by the Measure tools: pair measure (used for individual atom-atom distance) and multilateral measure (used for all atoms captured by a sphere).

QSAR

Using Property Plots to analyze QSAR properties:

MOPAC

Launching MOPAC 2002 computations

Charges

Mapping MOPAC 2002 charges on atoms using labels and colors

Other Features

• Molecular File formats
  The current version of BioAdviser for Windows supports the following file formats (by extension):
  BA - BioAdviser document - a native BioAdviser for Windows file format. Binary, proprietary format.
  PDB, ENT - Brookhaven Protein Data Bank file format (read/write).
  MOL - MDL molecular file format (read/write).
  HIN - HyperChem data file (read only).
  XYZ - A simple cartesian molecular file format (read/write).
  DAT - MOPAC Z-matrix files (read/write). MOPAC Cartesian format is available for writing.
  ARC - MOPAC ARC (archive) file (read only).
  WRL - VRML files (write only).
  PAR - BioAdviser repository files. Facilitates the modification of program repository definitions.
• File access methods
  Regular “File | Open” and “File | Open” in Fast Mode
  Drag & Drop
  Default Windows Open action for registered file types
• Embedded documents
  BioAdviser documents may be embedded in any Windows documents container like MS Word or Excel.
• Document/View architecture
  BioAdviser fully implements Document/View architecture and Multiple Document Interface.
• Color schemes for atoms and bonds.
  Default color scheme (Scheme1) - characterized by black carbon atoms.
  Alternate color scheme (Scheme 2) - characterized by white carbon atoms.
  Color by properties of atoms: partial charge, temperature factor.
  Color by properties of residue: residue charge, average temperature factor.
• Selections
  Multiple selection levels: Atoms, Residues, Molecules, Labels.
  Select All, Invert Selection operations.
  Narrowing the scope of the most operations to selected objects.
• Help system
  BioAdviser provides full, context-oriented help system.
• Bitmap generation
  Generation of High Resolution Bitmaps.

System requirements

Platforms

Microsoft Windows 98, 2000 or XP operating system
(DirectX graphics engine version 6 or higher required)
Hardware requirements

Suggested hardware configuration
Intel Pentium 1.0 GHz or higher
256 MB RAM or more
500MB HDD or more