SYBYL/Base

SemiChem products are available at http //www.semichem.com. AMPAC , available as a stand-alone product with Windows-based and workstation level interfaces, is a semiempirical quantum mechanical program featuring SAMI, AMI, MNDO, MNDO/d, PM3, MNDO/C, MINDO/3 semiempirical methods. AMPAC also includes a graphical user interface (GUI) that builds molecules and offers full visualization of results. The SYBYL/Base program offered by Tripos, Inc. (products described below) provides an interface with interactive graphing and structural display tools that can be used to access AMPAC s calculation tools. 

The Rekker approach is still used with revised Z/ systems, e.g., in the software program Z/SYBYL [8]. Over recent decades various other substructure-based approaches have been developed that are mostly implemented and available as computer programs. 

In addition, the calculation of many different ID, 2D and 3D descriptors is possible using a range of commercially available software packages, such as Sybyl, Cerius2, Tsar, Molconn-Z and Hybot. Several new descriptor sets are based on quantification of 3D molecular surface properties, and these have been explored for the prediction of, e.g., Caco-2 permeability and oral absorption. It is pointed out here that a number of these new descriptors are strongly correlated to the more traditional physico-chemical properties. 

Theoretical models include those based on classical (Newtonian) mechanical methods—force field methods known as molecular mechanical methods. These include MM2, MM3, Amber, Sybyl, UFF, and others described in the following paragraphs. These methods are based on Hook s law describing the parabolic potential for the stretching of a chemical bond, van der Waal s interactions, electrostatics, and other forces described more fully below. The combination assembled into the force field is parameterized based on fitting to experimental data. One can treat 1500-2500 atom systems by molecular mechanical methods. Only this method is treated in detail in this text. Other theoretical models are based on quantum mechanical methods. These include ... 

The second dataset consists of 50 V-acetyl peptide amides (Table 2) these peptides have un-ionizable side chains and have previously been studied by Buchwald and Bodor (28). The three-dimensional structures of the di-peptides were built using the force field and partial charges of Kollman (29) as implemented in Sybyl 6.5.3. The initial random starting conformations were energy minimized in vacuo. For all calculations described herein, the dielectric of the medium was set to unity and the electrostatic cut-off distance was set to 16 A. For each molecule, the Sybyl Genetic Algorithm-based conformational search,... 

By design, no conformational engine was implemented in DISCO, based on the assumption that at the time, no universal force fields and methods suitable for all types of compounds were available [53]. However, the commercial distributor Tripos provides access to 3D converters and conformational search engines such as Concord and Confort via the Sybyl interface. These algorithms will not be reviewed here as strictly seen they are not part of any pharmacophore identification program. The distance geometry approach has been used... 

The ligand-based alignments were carried out using the superposition program FlexS [2], and compound 4j as rigid template (in the conformation obtained by the docking) on the one site and the Multifit routine within the SYBYL software and the same template on the other site (Fig. 11.5). 

Fig. 11.5 Ligand-based alignments obtained applying the FlexS (a) and SYBYL Multifit (b) program. Compound 4j is colored magenta. 

The software used runs on most flavors of Unix and Linux. The procedures described here are intended for use on Unix-based systems. Commands are highlighted in boldface. In SYBYL, > signifies a selection of a menu-option, [] indicates a button to be pressed. 

Figure 1 Molecular model of a 12-base pair duplex of canonical B-form DNA. The two 12-mer strands that intertwine to form the duplex are colored separately (black and gray). Nucleic acid base pairs are stacked perpendicular to the helical axis at 3.4-A intervals (center-to-center distance), and the duplex helix repeats its spiral structure every 10 base pairs. (Figure provided by Dr. Carolyn Kanagy using the Sybyl Version 6.3 molecular modeling program from Tripos, Inc. and standard B-form DNA substructures.)...

Tel. 619-566-1127, fax 619-586-1481, e-mail haney netcom.com Hydropathic INTeraction by empirical calculation of atomistic hydrophobicity of molecules. Grid points based on energetics of hydrophobic and hydrophilic fields can be used for contouring a hydrophobic space and for scoring ligand-macromolecule and macromolecule-macromolecule interactions. Interfaced to SYBYL (CoMFA), Insight II, and Chem-X. Silicon Graphics and Evans 8c Sutherland ESV workstations. 

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