Atom-Type Description Language: a universal language to recognize atom types implemented in the VEGA program

The atom-type description language (ATDL) is a universal language used to describe and recognize the atom types from chemical connectivity. In this paper the ATDL approach specifications are reported with several examples. To date, this language is implemented in VEGA (http://www.ddl.unimi.it), a multipurpose program able to convert and manage several molecular file formats. This software uses the ATDL to assign the correct atom types in order to help several functions (file format conversion, molecular properties calculation, surface mapping and interaction energy analysis)

VEGA \u2013 An open platform to develop chemo-bio-informatics applications, using plug-in architecture and script programming

In this paper we present the expandability and flexibility features of the VEGA program (downloadable free of charge at http://www.ddl.unimi.it), for the development of custom applications, using it as a multipurpose graphical environment. VEGA can be customized using both plug-in architecture and script programming. The first is useful to add new features and functions, using homemade routines, written with the VEGA Plug-in Development Kit (SDK). With the second approach it is possible to design scripts in VEGA, using the REBOL language, in order to (1) add new functions or customize existing ones; (2) automate common procedures; and (3) allow network communications, by creating a bridge between VEGA and other applications (or other PCs) through the TCP/IP protocol

VEGA: a versatile program to convert, handle and visualize molecular structure on windows-based PCs

We here propose the program VEGA, that was developed to create a bridge between the most popular molecular software packages. In this tool some features are implemented some features to analyze, display and manage the three dimensional (3D) structure of the molecules. The most important features are (1) file format conversion (with assignment of the atom types and atomic charges), (2) surface calculation and (3) trajectory analysis. The executable and the source code can be free downloaded from http://users.unimi.it/ 3cddl

Modelling of binding modes and inhibition mechanism of some natural ligands of farnesyl transferase using molecular docking

Several natural inhibitors of farnesyl transferase have been reported in the literature: some compounds are competitive with farnesyl pyrophosphate (FPP), whereas other ones are competitive with Ras proteins, even though it is usually hard to highlight their inhibition mechanism, which is still unknown for several natural compounds. The aim of this work is to show that the molecular docking analysis can be successfully used to underline the inhibition mechanism of these natural compounds. First, the selected compounds were subjected to a detailed docking analysis, by means of BioDock, a program able to reveal the most likely binding mode for each ligand. By comparing these results with the binding sites for the natural substrates, earlier determined, it was possible to highlight the site specificity and the inhibition mechanism of the selected compounds. In addition, it is possible to relate the binding mode of these molecules with their lipole values, which is appreciably less for peptidomimetics than for FPP mimetic and reveals a straightforward method to predict and to understand the inhibition mechanism of these natural derivatives

Interactions of some PGHS-2 Selective Inhibitors with the PGHS-1: an Automated Docking Study by BioDock

The automated stochastic docking procedure BioDock has been applied to a series of inhibitors of PGH synthase, the key enzyme in the synthesis of eicosanoids from arachidonic acid. Some PGHS-2 selective inhibitors have been docked to the structure of the ovine PGHS-1 enzyme, as recently obtained by means of X-ray crystallographic analysis, in order to highlight possible structural bases for selectivity

Solvent constraints on the property space of acetylcholine. I. Isotropic solvents

The objective of this study was, first, to examine the property space of a test molecule and, second, to assess solvent constraints. Acetylcholine was chosen as the object of study given its interesting molecular structure and major biological significance. Molecular dynamics simulations of long duration (30 ns) were carried out with acetylcholine in a vacuum or in a box of solvent (chloroform, water, water plus one chloride counterion). For each of the 6000 conformers stored during each run, various geometric and physicochemical properties were calculated, namely, N+-C8 distance, solvent-accessible surface area (SAS), polar surface area (PSA), dipole moment, and lipophilicity (virtual log P). The variations of these properties as a function of the dihedral angles tau(2) and tau(3) were unexpectedly broad for such a small molecule. Dipole moment and virtual log P were well correlated, and they varied in a complex manner with the dihedral angles. For example, each of the seven conformational clusters was able to access much of the lipophilicity space of acetylcholine. Solvent constraints on the property space clearly indicate that a polar medium tends to favor polar conformers, whereas the opposite is true for a solvent of low polarity

The solute-solvent system: solvent constraints on the conformational dynamics of acetylcholine.

The objective of this study was to determine if and how a solvent influences internal motions in a solute molecule. Acetylcholine was chosen as the object of study given its interesting molecular structure and major biological significance. Molecular dynamics simulations were carried out in the vacuum (10 ns), water (5 ns), methanol (5 ns), and octanol (1.5 ns). Seven clusters of conformers were identified, namely, +g+g, -g-g, +gt, -gt, t+g, t-g, and tt, where the gauche and trans labels refer to the dihedral angles tau(2) and tau(3), respectively. As expected, the relative proportion of these conformational clusters was highly solvent-dependent and corresponded to a progressive loss of conformational freedom with increasing molecular weight of the solvent. More importantly, the conformational clusters were used to calculate instantaneous and median angular velocity (omega and omega(M), respectively) and instantaneous and median angular acceleration (alpha and alpha(M), respectively). Angular velocity and angular acceleration were both found to decrease markedly with increasing molecular weight of the solvent, i.e., vacuum (epsilon = 1) > water > methanol > octanol. The decrease from the vacuum to octanol was approximately 40% for tau(2) and approximately 60% for tau(3). Such solvent-dependent constraints on a solute's internal motions may be biologically and pharmacologically relevant