COMPUTATIONAL & MEDICINAL CHEMISTRY LAB

WET LAB

We have a well-equipped laboratory for organic chemistry recently renovated. In the lab they is available, typical glassware, vacuum pump, oven, two fridges, two flash-evaporators, one Buchi instrument for melting point determination, two available lab hoods for organic reaction experiments, pH-meter, etc. Department facilities available in routine basis: 400-MHZ and 200-MHz NMR instruments for 1D- and 2D-NMR experiments, FT-IR spectrometer. Available are also two LC-MS and one GS-MS instruments.

COMPUTATIONAL CHEMISTRY LAB

QUANTUM CHEMICAL AND MOLECULAR MECHANICS CALCULATIONS

GAUSSIAN - g09 (Linux) g03W (Windows XP). We are using this famous software as driving horse for running calculations to study structures or reaction meachanisms. Available are proven ab-initio methods (HF, post HF methods, DFT) with various basis sets (for example Pople's basis sets, Dunning's correlation consistent basis sets) and semi-empirical methods in the gas phase or using solvation models. Some molecular mechanics force fields can be also applied (Dreiding, UFF, AMBER). ONIOM method is available for the partition of a large system and calculation of the various parts at different levels of theory, for example mixed QM/MM calculations. The software implements molecular dynamics methods, transition state optimization routines etc (http://www.gaussian.com/).

HYPERCHEM (Windows XP). This software implements various quantum mechanical and molecular mechanics methods (MM+, Bio+, OPLS, AMBER). It is very useful because it includes a very friendly molecular modelling environment. A target model can be easily constructed and the program provides a variety of tools for the convenient manipulation of 3D structures (like changing chirality, reflection through planes, easy insertion of a variety of torsional constrains etc), the convenient model build of biological macromolecules (peptides, nucleotides) at a specific conformation (for example a-helix or beta-sheet, A-helix or B-helix form) etc. The molecular models can be optimized or simply used as input structures for calculations with GAUSSIAN software (http://www.hyper.com/).

PCMODEL (Windows XP). This software implements the very useful and well established molecular mechanics force fields MM3, MMX, MMFF94, OPLSAA, AMBER. It includes various conformational analysis methods (scan analysis, GMMX, Metropolis Monte Carlo) (http://www.serenasoft.com/).

MM3 and MM4 force fields(Linux). The original MM3 and MM4 forces fields of Allinger are available.

BIOMOLECULAR CALCULATIONS

MAESTRO-MACROMODEL (Linux). Far more than just a visualization program, Maestro also helps researchers organize and analyze data. Maestro's intuitive interface makes setting up calculations easy and straightforward. Computed results are automatically returned and incorporated into projects for further study. Maestro's vast array of visualization options makes it possible to glean insight into molecular properties as well as detailed intermolecular interactions. Maestro is a powerful and versatile molecular modeling environment, and the portal to the most advanced science in computational chemistry. MacroModel combines leading force fields, accurate effective solvation models, and advanced conformational searching methods to provide one of the most complete molecular modeling package suitable for a wide array of research (http://www.schrodinger.com/).

DESMOND (Linux). Desmond is a software package developed at D. E. Shaw Research to perform high-speed molecular dynamics simulations of biological systems. The code uses novel parallel algorithms and numerical techniques to achieve high performance and accuracy on platforms containing a large number of processors, but may also be executed on a single computer. Desmond includes code optimized for machines with an NVIDIA GPU. We are using extensively this software for running: a) MD simulations on general-purpose supercomputers and GPUs and b) FEP/MD simulations (https://www.deshawresearch.com /resources_desmond.html).

AMBER10 (Linux). Amber software is a set of molecular mechanical force fields for the simulation of biomolecules and a package of molecular simulation programs. We have used this program recently for running MM-PBSA calculations (http://ambermd.org/).

CHARMM (Linux). A molecular simulation program with broad application to many-particle systems with a comprehensive set of energy functions and a variety of enhanced sampling methods, and a range of implicit solvent models. We are using CHARMM for rescoring binding poses with the PBEQ module (https://www.charmm.org/charmm/).

GROMACS (Linux). GROMACS is a versatile package to perform molecular dynamics, i.e. simulate the Newtonian equations of motion for systems. We use it also extensively for analyzing trajectories and performing measures (http://www.gromacs.org/).

GOLD and AUTODOCK (Linux/Fedora 7). These programs predict how small molecules, like substrates or drug candidates, bind to a protein or receptor of known 3D structure - a problem of enormous significance in the rational drug design of drugs and combinatorial libraries.

GOLD (Genetic Optimisation for Ligand Docking)has won a lot of new users during the last few years because of its good results in impartial tests. Gold uses genetic algorithm to provide docking of flexible ligand and a protein with flexible hydroxyl groups. Otherwise the protein is considered to be rigid. Gold uses a scoring function that is based on favorable conformations found in Cambridge Structural Database and on empirical results on weak chemical interactions (http://www.ccdc.cam.ac.uk/products/life_sciences/gold/).

AUTODOCK uses Monte Carlo simulated annealing and Lamarckian genetic algorithm to create a set of possible conformations. LGA is used as a global optimizer and energy minimization as a local search method. Possible orientations are evaluated with AMBER force field model in conjunction with free energy scoring functions (http://autodock.scripps.edu/).

GOLDMINE (Linux/Fedora 7). GoldMine is a tool for the analysis and post-processing of docking results. (http://www.ccdc.cam.ac.uk/products/life_sciences/goldmine).

CHIMERA (Linux/Fedora 7). UCSF Chimera is a highly extensible program for interactive visualization and analysis of molecular structures and related data, including density maps, supramolecular assemblies, sequence alignments, docking results, trajectories, and conformational ensembles. High-quality images and animations can be generated (http://www.cgl.ucsf.edu/chimera/).

PYMOL (Linux). PyMOL is open-source molecular visualization system which is effective (https://www.pymol.org/).

VMD (Linux). VMD is used extensively in our lab for visualization, and analysis of biological systems (http://www.ks.uiuc.edu/Research/vmd/).

WITNOTP (Linux). This is very useful graphics tool developed by A. Widmer at Novartis for preparing input structures for AMBER, CHARMM etc (http://www.biochem-caflisch.uzh.ch/download/).

HARDWARE

We have available three 8-cores CPU workstations with GPU cards for acceleration of MD simulation production runs, two 8-cores CPU workstations and one 16-cores CPU workstations for running FEP/MD and QM calculations with GAUSSIAN.

In most of cases resources (CPU and GPU hours) are available from supercomputers.

We have available two PCs used for routine daily procedures like office work, transferring NMR spectra from the NMR spectrometers etc.