ASCONA is a fully automated command line tool for generating sequence alignments and superpositions of protein binding sites. Itisgeared to the alignment of alternative protein conformations and especially addresses the tasks of dealing with highly flexible backbone regions, detecting multiple occurrences of a binding site in oligomeric structures, and coping with arbitrary annotation inconsistencies and structural artifacts.

Publikationen

1. Bietz, S.; Rarey, M. (2015) ASCONA: Rapid Detection and Alignment of Protein Binding Site
   Conformations . Journal of Chemical Information and Modeling, 55(8):1747–1756.

Conformator is a novel conformer ensemble generator that stands out by its handling of macrocycles, high accuracy, as well as robustness with respect to input formats and molecular geometries. With an extended set of rules for sampling torsion angles, a novel algorithm for macrocycle conformer generation, and a new clustering algorithm for the assembly of conformer ensembles, Conformator generates high-quality conformation ensembles.

The Connected Subgraph Fingerprint (CSFP) is a novel fingerprint method which, in contrast to other methods, captures all connected subgraphs as structural features of a compound. This property gives the CSFP a complete feature space and high adaptive potential. Apart from surpassing common methods in standard similarity-driven virtual screening settings, the CSFP has substantial structural advantages when applied to combinatorial fragment spaces or in machine learning.

Publikationen

1. Bellmann, L.; Penner, P.; Rarey, M. (2019) Connected Subgraph Fingerprints: Representing Molecules Using Exhaustive Subgraph Enumeration . Journal of Chemical Information and Modeling, 59 (11):4625-4635.

The electron density score for individual atoms (EDIA) quantifies the electron density fit of each atom in a crystallographically resolved structure. Multiple EDIA values can be combined with the help of the power mean to compute EDIAm, the electron density score for multiple atoms to score a set of atoms such as a ligand, a residue, or an active site.

Publikationen

1. Meyder, A.; Nittinger, E.; Lange, G.; Klein, R.; Rarey, M. (2017) Estimating Electron Density Support for Individual Atoms and Molecular Fragments in X-ray Structures . Journal of Chemical Information and Modeling, 57(10):2437–2447.

The fragment space exhaustive enumeration system (FSees) is an efficient method for exhaustively enumerating all molecules within a certain molecular subspace. This chemical space is described as a fragment space and constrained by a set of user-defined physicochemical properties. The FSees algorithm uses file-based data structures to overcome the limitation of computer main memory thus allowing to enumerate very large chemical spaces. The resulting chemical library can be used as a starting point for computational lead-finding technologies, like similarity searching, pharmacophore mapping, docking, or virtual screening.

Feature Trees (FTrees) is a molecular descriptor based on the idea of reduced graphs. A molecule is represented via the covalent structure of its building blocks. The comparison of molecules based on FTrees enables scaffold hopping, since the chemical structure of each building block is of less importance. FTrees can be used for combinatorial searching in fragment spaces (FTrees-FS). 
The necessary double-dynamic programming strategy is the only method available today enabling a precise and deterministic search for similar molecules in fragment spaces. FTrees and FTrees-FS are licenced via BioSolveIT GmbH. 

Also based on FTrees, the Software LoFT for designing chemical libraries based on fragment spaces was developed.

Publikationen

1. Fischer, J. R., Lessel, U., Rarey, M. (2011) Improving Similarity-Driven Library Design: Customized Matching an Regio-Selective Feature Trees . Journal of Chemical Information and Modeling, 51(9):2156–2163.
2. Fischer, J.R., Lessel, U., Rarey, M. (2010) LoFT: Similarity-Driven Multi-Objective Focused Library Design . Journal of Chemical Information and Modeling, 50(1):1-21.
3. Fischer, J. R., Rarey, M. (2007) SwiFT: an index structure for reduced graph descriptors in virtual screening and clustering . Journal of Chemical Information and Modeling, 47(4):1341-53.
4. Rarey, M., Stahl, M. (2001) Similarity Searching in Large Combinatorial Chemistry Spaces . Journal of Computer-Aided Molecular Design, 15:497-520.
5. Rarey, M., Dixon, J.S. (1998) Feature Trees: A new molecular similarity measure based on tree matching . Journal of Computer-Aided Molecular Design, 12:471-490.

HYDE is a novel method to estimate the energetics of protein-ligand complexes. The HYDE function is calibrated using octanol-water partition coefficients (logP values) and consistently describes hydrogen bonds, dehydration and the hydrophobic effect. The patented HYDE technology is developed in a collaboration with Bayer CropScience and the BioSolveIT GmbH. HYDE is part of the LeadIT software suite (BioSolveIT GmbH).

Publikationen

1. Schneider, N., Klein, R., Lange, G., Rarey, M. (2012) Nearly no Scoring Function without a Hansch-Analysis . Molecular Informatics, 31(6-7):503–507.
2. Schneider, N., Hindle, S., Lange, G., Klein, R., Albrecht, J., Briem, H., Beyer, K., Claußen, H., Gastreich, M., Lemmen, C., Rarey, M. (2011) Substantial improvements in large-scale redocking and screening using the novel HYDE scoring function . Journal of Computer-Aided Molecular Design, 26(6):701-723.
3. Reulecke, I., Lange, G., Albrecht, J., Klein, R., Rarey, M. (2008) Towards an integrated description of hydrogen bonding and dehydration: II. Reducing false positives in virtual screening using the HYDE scoring function . ChemMedChem, 3(6):885-897.

Mona is an interactive tool that can be used to prepare and visualize large small-molecule datasets. A set centric workflow allows to intuitively handle hundred thousands of molecules. Building upon the robust framework Naomi common cheminformatics tasks such as analysis, filtering and converting of  molecular files can be performed with high efficiency.

Publikationen

1. Matthias Hilbig;
   Matthias Rarey (2015) MONA 2: A Light Cheminformatics Platform for Interactive
   Compound Library Processing . Journal of Chemical Information and Modeling, 55(10):2071–2078.
2. Hilbig, M.; Urbaczek, S.; Groth, I.; Heuser, S.; Rarey, M. (2013) MONA - Interactive manipulation of molecule collections . Journal of Cheminformatics, 5 (38)

NAOMI is a command-line tool for the consistent conversion of common chemical file formats (SDF, SMILES, MOL2). It is based on a robust chemical model which is designed to appropriately describe organic molecules relevant. NAOMI also checks the chemical validity of molecules and calculates hydrogen coordinates. In June 2016, NAOMI was replaced by our powerful universal converter named UNICON.

Publikationen

1. Urbaczek, S., Kolodzik, A., Fischer, J. R., Lippert, T., Heuser, S., Schulz-Gasch, T., Rarey, M. (2011) NAOMI: On the Almost Trivial Task of Reading Molecules
   from Different File formats . Journal of Chemical Information and Modeling, 51(12):3199-3207.

NAOMInext is a software tool supporting medicinal chemists during hit-to-lead optimization. Starting from a co-crystallized small fragment, synthetic feasible lead compounds are generated directly within the proteins binding site. Thus, the software implicitly perfoms target-focused library design.

Publikationen

1. Sommer, K.; Flachsenberg, F.; Rarey, M. (2018) NAOMInext - Synthetically feasible fragment growing in a structure-based design context . European Journal of Medicinal Chemistry, 163:747-762.

NAOMInova is a software tool enabling the geometrical and chemical analysis of atoms surrounding a user-defined structure of interest. Based on a user-selected set of protein structures, substructures can be searched and the distribution of partner points can be visualized. Two visualization options are available: the „set“ visualization, i.e. the partner points surrounding the substructure, and the „pocket“ visualization, i.e. the transformation of all partner points surrounding the substructure into a suitable active site of interest. Diverse geometric - distance, angles, resolution - and chemical - atom type, location, amino acid - properties can be selected for further analysis. Additionally, for each partner point the original complex is stored, which allows an easy evaluation whether this point is of interest for the user or not.

PELIKAN is a software tool enabling rapid searching of spatial interaction patterns in large collections of protein-ligand complexes. Data from protein-ligand complexes is stored in an SQLite database which can be subject to different search processes.

The PELIKAN software package comes with a graphical user interface, providing dialogs to build SQLite databases from any set of protein-ligand complexes and allowing the convenient construction of 3D queries starting from a protein-ligand interface of interest or from scratch. The results of a search are shown in a 3D viewer.

PoseView automatically generates two-dimensional diagrams of complexes with a focus on the interaction pattern between ligand and protein. Interactions between the molecules are estimated by a built-in interaction model that is based on atom types and simple geometric criteria. The quality of the resultant diagrams is comparable to hand-drawn examples from textbooks and scientific publications.

PoseView @ PDB

Publikationen

1. Stierand, K., Rarey, M. (2010) Drawing the PDB - Protein-Ligand Complexes in two Dimensions . Medicinal Chemistry Letters, 1(9):540-545.
2. Stierand, K., Rarey, M. (2007) From Modeling to Medicinal Chemistry: Automatic generation of two-dimensional complex diagrams . ChemMedChem, 2(6):853-860.
3. Stierand, K., Maaß, P. C., Rarey, M. (2006) Molecular Complexes at a Glance: Automated Generation of two-dimensional Complex Diagrams . Bioinformatics, 22(14):1710-1716.

ProToss is a fully automated hydrogen prediction tool for protein-ligand complexes. It adds missing
hydrogen atoms to protein structures (PDB-format) and detects reasonable protonation states,
tautomers, and hydrogen coordinates of both protein and ligand molecules.

Publikationen

1. Bietz, S.; Urbaczek, S.; Schulz, B.; Rarey, M. (2014) Protoss: a holistic approach to predict tautomers and protonation states in protein-ligand complexes . Journal of Cheminformatics, 6(12):1-12.
2. Lippert, T., Rarey, M. (2009) Fast automated placement of polar hydrogen atoms in protein-ligand complexes . Journal of Cheminformatics, 1(13)

RAISE is the short form of RApid Index-based Screening Engine. Based on triangle descriptor representations of ligands and protein active sites, highly efficient screening is enabled. The cRAISE software allows classic virtual screening of finding ligands for one protein target. The iRAISE software covers the reverse scenario and thus allows inverse virtual screening, where for potential protein targets of one small molecule are identified.

Recore is an index-driven software system for rescaffolding. Starting with a bioactive molecule, parts of it can be interactively marked and replaced by geometrically fitting fragments. Recore enables the consideration of pharmacophoric constraints. Via connection to the Cambridge Cristallographic 
Database (CSD), low-energy conformations are created. The indexing technology allows nearly interactive work. Recore is part of the LeadIT sofware plattform (BioSolveIT GmbH).

Publikationen

1. Maaß, P., Schulz-Gasch, T., Stahl, M., Rarey, M. (2007) Recore: A fast and Versatile Method for Scaffold Hopping Based on Small Molecule Crystal Structure Conformations . Journal of Chemical Information and Modeling, 47(2):390-399.

SIENA is a software pipeline enabling the fully automated construction of protein structure ensembles from the PDB. Starting with a single query structure, all binding sites with high sequence similarity are extracted from the PDB, aligned, and protonated. SIENA is able to deal with complicated cases like binding sites at protein domain interfaces or within homo-multimeric proteins.

Publikationen

1. Bietz, S.; Rarey, M. (2016) SIENA: Efficient Compilation of Selective Protein Binding Site Ensembles . Journal of Chemical Information and Modeling, 56(1):248-59.
2. Bietz, S.; Rarey, M. (2015) ASCONA: Rapid Detection and Alignment of Protein Binding Site
   Conformations . Journal of Chemical Information and Modeling, 55(8):1747–1756.

The SMARTScompareViewer and the accompanying SMARTScompare command line tool offer chemical pattern comparisons for the SMARTS language. SMARTScompare determines similarity and subset relations between SMARTS-patterns.

Publikationen

1. Ehmki, E.S.R.; Schmidt, R.; Ohm, F.; Rarey, M. (2019) Comparing Molecular Patterns Using the Example of SMARTS: Applications and Filter Collection Analysis . Journal of Chemical Information and Modeling, 59(6):2572-2586.
2. Schmidt, R.; Ehmki, E.S.R.; Ohm, F.; Ehrlich, H.-C.; Mashychev, A.; Rarey, M. (2019) Comparing Molecular Patterns Using the Example of SMARTS: Theory and Algorithms . Journal of Chemical Information and Modeling, 59(6):2560-2571.

The SMARTSeditor is a graphic editing tool for generic chemical patterns. Based on the SMARTS language, chemical patterns can be created and edited interactively, similar to molecule editing in a chemical structure editor. The SMARTSeditor supports editing of given SMARTS or editing of chemical pattern without knowledge of the SMARTS language from scratch. It supports logic combinations as well as atom environment definitions. The generated pattern is converted into a SMARTS string which can be used in any application where the pattern is needed, e.g. for filtering of molecule databases.

Publikationen

1. Bietz, S.; Schomburg, K. T.; Hilbig, M.; Rarey, M. (2015) Discriminative Chemical Patterns: Automatic and Interactive Design . Journal of Chemical Information and Modeling, 55(8):1535–1546.
2. Schomburg, K., Wetzer, L., Rarey, M. (2013) Interactive design of generic chemical patterns . Drug Discovery Today, 13:1-8.

SpaceCompare is a novel tool for the comparison and analysis of ultra-large combinatorial chemical spaces. It enables the complete examination of trillion-sized chemical spaces for the first time by employing a combinatorial algorithmic approach. The tool has three modes of operation

- overlap calculation of two combinatorial spaces
- distribution computation for five well-known  physicochemical properties
- chemical space optimization by removal of fragments with undesired properties

SpaceLight is a novel search method for similarity-driven virtual screening in large combinatorial fragment spaces using topological fingerprints. It utilizes the well-known ECFP and the Connected Subgraph Fingerprint (CSFP) to describe molecular similarity. In contrast to existing workflows using fingerprint methods, the SpaceLight approach is able to exploit the combinatorial character of fragment spaces and consequently can conduct similarity searches considering billions of compounds within seconds on a standard PC. In addition fragments forming scaffolds can be retreived to identify reaction routes for compounds and custom fragment spaces can be generated.

Publikationen

1. Bellmann, L.; Penner, P.; Rarey, M. (2021) Topological Similarity Search in Large Combinatorial Fragment Spaces . Journal of Chemical Information and Modeling, 61(1):238-251.

SpaceMACS is a novel search method for similarity-driven virtual screening in large combinatorial fragment spaces. SpaceMACS identifies maximum common connected induced substructures between a query and all products of a fragment space, like commercial make-on-demand libraries. SpaceMACS heavily exploits the fragment structure of those spaces screening billions or even trillions of compounds within seconds to minutes on standard desktop computers. Runtimes depend on the number of results retrieved and the size of the fragment space representation. In general, they are mostly independent of the number of compounds represented. In order to explore fragment spaces, the SpaceMACS tool supports interactive command line sessions and processing of multiple queries avoiding the need to load the space for every single query.

Publikationen

1. Schmidt, R.; Klein, R.; Rarey, M. (2021) Maximum Common Substructure Searching in Combinatorial Make-on-Demand Compound Spaces . Journal of Chemical Information and Modeling, 62(9):2133–2150.

Three-dimensional protein structures play a vital role in drug design. Thorough examination of the available data before usage in experimentation and method validation is highly recommended. StructureProfiler assists in automatically profiling structures ranging from model characteristics like low R factor over active site features such as bond lengths in expected ranges to ligand properties such as electron density coverage and frequently seen torsion angles.

Publikationen

1. Meyder, A.; Kampen, S.; Sieg, J.; Fährrolfes, R.; Friedrich, N.-O.; Flachsenberg, F.; Rarey, M. (2018) StructureProfiler: An all-in-one Tool for 3D Protein Structure Profiling . Bioinformatics, 35(5):874-876.

The Torsion Analyzer is a graphical tool for the analysis of torsion angles in small molecule conformations. It is based on an expert-derived collection of SMARTS patterns and rules. Rules result from statistical analysis of histograms derived from small molecule X-ray data. Rotatable bonds of molecules loaded into the Torsion Analyzer are color-coded on the fly by means of a traffic light system highlighting regular, borderline and unusual torsion angles.

Publikationen

1. Guba, W.; Meyder, A.; Rarey, M.; Hert, J. (2016) Torsion Library Reloaded: A New Version of Expert-Derived SMARTS rules
   for Assessing Conformations of Small Molecules . Journal of Chemical Information and Modeling, 56(1):1-5.
2. Schärfer, C., Schulz-Gasch, T., Ehrlich, H.C., Guba, W., Rarey, M., Stahl, M. (2013) Torsion Angle Preferences in Drug-like Chemical Space: A Comprehensive Guide . Journal of Medicinal Chemistry, 56 (6):2016-28.
3. Schulz-Gasch, T., Schärfer, C., Guba, W., Rarey, M. (2012) TFD: Torsion Fingerprints As a New Measure To Compare Small
   Molecule Conformations . Journal of Chemical Information and Modeling, 52(6):1499−1512.

UNICON is a command-line tool to cope with common cheminformatics tasks. The functionality of UNICON ranges from file conversion between standard formats SDF, MOL2, SMILES, and PDB via the generation of 2D structure coordinates and 3D structures to the enumeration of tautomeric forms, protonation states and conformer ensembles.