HyperChem 8.0

Building molecules with HyperChem is simple: just choose an element from the periodic table, and click and drag with the mouse to sketch a structure.

Mouse control of rotation around bonds,stereochemistry, and "rubber banding" of bonds makes changing structures easy.

Extensive selection, highlighting, and display capabilities make it easy to focus on areas of interest in complex molecules.

You can...

• Select, rotate, translate, and resize structures with convenient mouse controlled tools. Modify settings to control operation of tools
• Convert rough sketches into 3D structures with HyperChem's model builder
• Apply builder constraints easily: specify bond lengths, bond angles, torsion angles, or the bonding geometry about a selected atom
• Specify atom type, atom charge, formal charge and atomic mass
• Build clusters and complex molecular assemblies; move individual atoms and molecules as easily as you move groups
• Build peptides and nucleic acids from amino acid and nucleotide residue libraries
• Mutate residues and build large molecules incrementally (make changes at any point)
• Add a periodic box of pre-equilibrated water molecules for aqueous solvation studies. Periodic boundary conditions can be used with other solvent systems, or without solvents
• Import structures from standard file formats: Brookhaven PDB, ChemDraw CHM, MOPAC Z-matrix, MDL MOL and ISIS Sketch, and Tripos MOL2 files

Molecular Display

• Display structures using ball and stick, fused CPK spheres, sticks, van der Waals dots, and sticks with vdW dots; switch easily between rendering styles
• Specify shading and highlighting, stick width, and the radii of spheres. Stereo and perspective viewing are also available
• Display a Ray Traced image of the molecules in the workspace
• Select and name sets of atoms for custom display or monitoring of properties
• Set and display custom labels for atoms
• Display bond labels showing the current bond length or the currently computed quantum mechanical bond order
• Display protein backbones using ribbons, with optional display of sidechains
• Highlight potential hydrogen bond interactions
• Display dipole moment vectors and gradient vectors

Computational Chemistry

Use HyperChem to explore quantum or classical model potential energy surfaces with single point, geometry optimization, or transition state search calculations. Include the effects of thermal motion with molecular dynamics, Langevin dynamics or Metropolis Monte Carlo simulations. User defined structural restraints may be added

Types of Calculations

• Single point calculations determine the molecular energy and properties for a given fixed geometry
• Geometry optimization calculations employ energy minimization algorithms to locate stable structures. Five minimization algorithms are provided
• Vibrational frequency calculations find the normal vibrational modes of an optimized structure. The vibrational spectrum can be displayed and the vibrational motions associated with specific transitions can be animated
• Transition state searching locates the metastable structures corresponding to transition states using either Eigenvector Following or Synchronous Transit methods. Molecular properties are then calculated
• Molecular dynamics simulations compute classical trajectories for molecular systems. Quantum forces can be used to model reactive collisions. Heating, equilibration, and cooling periods can be employed for simulated annealing and for studies of other temperature dependent processes. Both constant energy and constant temperature simulations are available
• Langevin dynamics simulations add frictional and stochastic forces to conventional molecular dynamics to model solvent collisional effects without inclusion of explicit solvent molecules
• Metropolis Monte Carlo simulations sample configurations from a statistical ensemble at a given temperature and are useful for exploring the possible configurations of a system as well as for computing temperature dependent equilibrium averages

Computational Methods

Ab Initio Quantum Mechanics

• Choose from many commonly used basis sets (STO-1G to D95**) including the standard STO-3G, 3-21G, 6-31G*, and 6-31G** basis sets
• Extra basis functions ( s, p, d, sp, spd ) can be added to individual atoms or to groups of atoms
• Users can also define their own basis sets or modify existing basis sets easily using HyperChem's documented basis set file format

Semi-empirical Quantum Mechanics

• HyperChem offers ten semi-empirical molecular orbital methods, with options for organic and main-group compounds, for transition metal complexes, and for spectral simulation
• Choose from Extended Huckel, CNDO, INDO, MINDO/3, MNDO, MNDO/d, AM1, PM3 (including transition metals), ZINDO/1 and ZINDO/S

Molecular Mechanics

• Four force fields provide computationally convenient methods for exploring the stability and dynamics of molecular systems
• Added flexibility of user defined atom types and parameters
• Choose from MM+, a general purpose force field, and three specialized biomolecule force fields: Amber, BIO+, and OPLS

Mixed Mode Calculations

• HyperChem allows you to perform quantum calculations on part of a molecular system, such as the solute, while treating the rest of the system classically. This boundary technique is available for all the quantum methods, with some limits for ab initio calculations

Results with HyperChem

• Rendering choices: Ball-and-stick, fused CPK spheres with optional shading and highlighting. Also vdW dots, cylinders and overlapping spheres
• Ribbon rendering for protein backbones, with optional sidechain display
• 3D Isosurfaces or 2D contour plots of: total charge density, molecular orbitals, spin density, electrostatic potential (ESP), ESP mapped onto 3D charge density surface
• Isosurface rendering choices: wire mesh, Jorgensen-Salem, transparent and solid surfaces, Gouraud shaded surface. User specified grid and isosurface value
• During simulations, display and average kinetic, potential, and total energy, as well as values of user specified bond lengths, bond angles, or torsion angles.
• Animate vibrational modes
• Display2D or 3D potential energy plots

Customize and Automate

• Construct custom menus
• Automate routine operations with scripts
• Send selected data to files or workspace
• Add new features as menu items, or run from scripts

Predict

• Relative stabilities of isomers
• Heats of formation
• Activation energies
• Atomic charges
• HOMO-LUMO energy gap
• Ionization potentials
• Electron affinities
• Dipole moments
• Electronic energy levels
• MP2 electron correlation energy
• CI excited state energy
• Transition state structures and properties
• Non-bonded interaction energy
• UV-VIS absorption spectra
• IR absorption spectra
• Isotope effects on vibrations
• Collision effects on structural properties
• Stability of clusters

Save Results

• Use Import/Export option to save results of quantum mechanics calculations or to view results generated by other programs
• Use HyperChem Data to store structures and properties in a custom molecular database
• Create Reaction Movies in AVI format
• Save as HTML page to store and display teh structure, orbitals, IR and UV spectra and IR spectra with normal modes

Integrated Modules

RAYTRACE

The Raytrace module enables you to create stunning raytraced images of molecules in the workspace by bridging with the very high-level graphics visualization application known as Persistence of Vision (POV) Ray for Windows.

• Automatically generate POV-Ray input files describing the molecule.
• Run POV-Ray to generate high quality images in any of several graphic file formats supported by POV-Ray

RMS Fit

RMS Fit provides a new tool for comparing structures of molecules in HyperChem, augmenting the existing overlay function and the flexible fitting provided by restrained optimizations.

The RMS Fit module lets you carry out the following tasks:

• • Overlay two molecules by minimizing the distance between corresponding atoms in the two target molecules, displaying the residual error
• • Have the corresponding atoms be all atoms, or selected atoms only
• • Designate the corresponding atoms by their numbering within a molecule, or by the order in which you select them

SEQUENCE EDITOR

Sequence Editor provides additional tools for manipulating strings of amino acids in HyperChem. The Sequence Editor brings the following capabilities to HyperChem:

• Read FASTA files consisting of strings of one-letter amino acid designators
• Specify secondary structure, including alpha helix, extended, parallel and anti-parallel beta sheets, three types of beta turns, and random coil, and put the resulting structure into HyperChem
• Get polypeptides from HyperChem with secondary structure designators
• Search for specific amino acid sequences in a polypeptide
• Show the polarity of each amino acid in the sequence, and display the distribution of each type
• Compare the similarity of two polypeptides, using a Dayhoff matrix (dot plot) approach

CRYSTAL BUILDER

With Crystal Builder you can build up crystals in HyperChem by hand, by entering fractional coordinates, or choose from a set of samples provided. Crystal Builder gives you control over the face you view, and the size of the crystal you build; it also allows you to read Cambridge Crystal Database files into HyperChem. The Crystal Builder includes the following features:

• Read in Cambridge Crystallographic Database files (FDAT), and place them in HyperChem
• Over 20 sample crystal structures included, particularly useful in educational contexts
• Control crystal size and shape (number of unit cells in each direction).
• Control which crystal face you view, by specifying Miller indices
• For manual building of crystals, you can specify unit cell angles and lengths (a, b, c) for each of the eight basic crystal types, plus face centered cubic and body-centered cubic. All distinct space groups are not included, so you may need to calculate special positions as required for the different space groups

SUGAR BUILDER

With Sugar Builder you can construct polysaccharides from individual saccharide components. The Sugar Builder's features include the following:

• Build polysaccharides from aldoses and ketoses, as well as amino sugars and N-acyl sugars, Inositol and deoxy sugars
• Terminate the polysaccharides using any of the thirteen blocking groups provided
• For each saccharide, you have control over the isomer (D or L), the form (acyclic, a, or b), the angles (f, y and w), and the connection site.
• Construct polymers from other, possibly non-saccharide, components using the user-defined component dialog box
• Link polysaccharide strands, with full specification of site and angles
• Carry out simulations, using an extension of the AMBER force field specifically intended for saccharides [S. W. Homans, Biochemistry 29, 9110 (1990)]. This force field allows you to carry out calculations on some, but not all, polysaccharides. (HyperChem's MM+ force field will also compute properties of polysaccharides).

CONFORMATIONAL SEARCH

The Conformational Search module is a tool for finding and saving stable structures of molecules, using stochastic approaches based on modification of torsion angles.

Conformational Search has a wide range of options to tune the search for your particular needs. The general approach is to twist selected torsion angles of the system to distort a structure and, if certain tests are met, optimize to obtain a new candidate structure. The new structure can be accepted or rejected as a structure of interest according to a variety of criteria. Here is a list of some of the more important facilities of Conformational Search:

• Select the torsion angles you wish to vary using HyperChem's selection methods
• Study ring flexibility using our implementation of the torsional flexing method of Kolossvary and Guida [J. Comput. Chem., 14, 691, (1993)].
• Choose between random walk and a usage-directed approach [G. Chang, W. C. Guida and W. C. Still, J. Am. Chem. Soc., 111, 4379 (1989)] to generate a sequence of conformations
• Save all acceptable structures as the run progresses, and restart previous searches
• Filter structures prior to optimization by checking for close contacts and torsion angles that are similar to previously optimized structures, and after optimization for inversion of chiral centers
• Following optimization, eliminate duplicate structures by comparing energies, torsion angles, and RMS fit residual errors, automatically taking account of user specified equivalent atoms
• Save full details of the search to a file. Structures can be read back in and put into HyperChem by simply selecting the structure of interest and executing a single command
• Display results in tables that can be copied into spreadsheets for further analysis

QSAR PROPERTIES

QSAR Properties allows calculation and estimation of a variety of molecular descriptors commonly used in Quantitative Structure Activity Relationship (QSAR) studies. Most of the methods were developed for and are primarily applicable to organic molecules.

Here are some of the properties you can estimate using QSAR Properties:

• Atomic charges, using the Gasteiger-Marsili method [Tetrahedron, 36, 3219 (1980)]
• Van der Waals and solvent accessible surface areas, using a rapid, approximate method due to W. C. Still and coworkers [W. Hasel, T. F. Hendrickson, W. C. Still, Tet. Comput. Meth., 1, 103 (1988)], or using a slower grid based method
• Molecular volumes, bounded by Van der Waals or solvent accessible surfaces, using a grid method
• Hydration energy (for peptides and similar systems), using our implementation of a method parametrized by Scheraga et al. [T. Ooi, M. Oobatake, G. Nemethy and H. Scheraga, Proc. Natl. Acad. Sci. USA 84, 3086 (1987)], based on the approximate surface area calculation
• Log P (the log of the octanol-water partition coefficient), a hydrophobicity indicator, using our implementation of an atom fragment method developed by Ghose, Pritchett and Crippen [J. Comput. Chem., 9, 80 (1988)]. For a sample of organic molecules, the method yields a correlation coefficient (r) with experimental values of 0.92 and a standard error of 0.36
• Refractivity, also using an atom-based fragment method due to Ghose and Crippen [J. Chem. Inf. Comput. Sci., 27, 21 (1987)]. For a sample of organic molecules, the method yields a correlation coefficient (r) with experimental values of 0.995 and a standard error of 1.1
• Polarizability, using an atom-based method due to K. J. Miller [J. Am. Chem. Soc., 112, 8533 (1990)]. For a sample of organic molecules, the method yields a correlation coefficient (r) with experimental values of 0.991 and a standard error of 9.3
• Mass, using a straightforward method
• QSAR Properties can compute the property for the current system in HyperChem, or operate in standalone mode with HyperChem Input (HIN) files
• Carry out batch calculations directly from spreadsheets supporting Windows Dynamic Data Exchange, using the spreadsheet macro language
• Send results to a results window, and save to a log file

SCRIPT EDITOR

HyperChem's scripting capability is one of its most versatile features, allowing it to be controlled from outside using scripts or external programs. The Script Editor is a tool to assist you in developing scripts in the HyperChem language, and to send script messages directly to HyperChem as a command line

Script Editor's features include the following:

• Send script messages directly to HyperChem using a command line.
• Paste script messages from a dialog box, which lists all available script messages
• Read in your existing script files, and save lists of messages for later use
• Execute any number of script messages
• Retrieve information from HyperChem, display it in a window, and save it to a file. Results of calculations, or details of the current molecular system, can be saved in this manner

New Force Fields

HyperChem added significant new capability to the AMBER method of molecular mechanics by including up-to-date modifications of this force field. AMBER code supports 5 parameter sets with their associated functional forms:

• Amber 2
• Amber 3
• Amber for saccharides
• Amber 94
• Amber 96
• Amber 99

Default Parameter Scheme for AMBER and OPLS

Any AMBER or OPLS computation can continue computing with default parameters, when explicit parameters are missing from the relevant parameter file. The normal AMBER and OPLS parameter scheme fails when explicit parameters associated with "atom types" are not available. with default parameters, no calculation fails for lack of parameters.

ESR Spectra

Calculated values of Hyperfine Coupling constants are also available, for characterizing the ESR spectra of open shell systems.

Electric Polarizabilities

Computation of polarizability tensors is available.

Plots of Potential Energy

You can select one or two structural features (bond length, torsion angle etc.) and request a plot of the potential energy as a function of either a single structural feature (2D plot) or two structural features (3D plot).

Protein Design

You can cut and paste any amino acid sequence. That is, a piece can be cut out, a piece inserted, or a sequence of one length replaced by a new sequence of a different length. Annealing operations are, of course, required for the rest of the protein to adapt to these modifications.

Electric Fields

It is possible to superimpose an applied electric field on any calculation. For example, a charged system will now drift in the workspace during a molecular dynamics run if an external electric field has been applied. Studying molecular behavior in an electric field is now possible.

Annotations

While it has always been possible to copy the rendering of molecules in HyperChem into a file or onto the clipboard and then transfer the rendering into a drawing or painting program to prepare overhead transparencies or other presentation material, directly creating such material without leaving HyperChem is now possible.

An annotation in HyperChem is a length of text that can be placed anywhere in the workspace. Because the text can have attributes such as a font, a color, and a size, it is possible to create annotations such as arrows, lines, circles, rectangles and any number of other drawing primitives. Annotating the molecules that are being modeled in HyperChem allows you to print the workspace and more easily describe to others the results of your modeling.

HyperChem contains a number of features associated with creating and manipulating these annotations. Because they exist in a plane or layer that is independent of the molecular or modeling plane, they augment rather than collide with the modeling of earlier versions of HyperChem. At the same time by being able to show or print both planes at the same time, a rich set of annotation options is possible.

While that is not the primary intent, HyperChem could now be used to prepare illustrations independent of chemistry and molecular modeling.

Charge and Multiplicity are Saved

The total charge and spin multiplicity are now stored in the HIN file and are restored when a molecular HIN file is read. Earlier, these had to be set interactively for any new molecule in the workspace.

Drawing Constraints

It is now possible to constrain your drawing of 2D molecules so that the the resultant drawn molecule has uniform bond lengths and angles and resembles a standard 2D molecular representation as might be seen in textbooks. These constraints have no effect on the subsequent 2D to 3D model building.

Graphical Display of Gradients

It is possible to visualize the gradient (force) on any atom as a vector. Any set of atoms can display these vectors.

Bond Labels

A set of dynamically updated labels are available for bonds as well as atoms and residues. These bond labels can be one of; Bond length or Bond order - as calculated quantum mechanically

Enhanced Selection Capability

HyperChem operations depend to a great extent on one’s ability to select a subset of atoms. For example, it is possible to select atoms based on the range of various computed quantities such as their atomic charge or atomic gradient. Thus, for example, one can now select all atoms with a charge between -0.1 and 0.1.

The atom selection options are organized as either a selection based on a "string" property of an atom, such as the atom type (e.g. CH), or a "number" property such as the atom charge described above.