Protein & Antibody Modeling

MOE's CASP validated applications for protein structure prediction are powerful, intuitive and easy to use, both for experts and occasional users. Powerful homologue identification, alignment technology and refinement methodology make high quality sequence to structure predictions routinely possible.

Use Protonate3D to assign optimal free energy proton geometry and ionization states to macromolecular systems to improve the results of simulations, docking and active site analyses. Macromolecules, ligands, solvent and metals are assigned protonation states using a Generalized Born electrostatics model. Tautomer, titration and conformation states are determined simultaneously using a sophisticated Unary Quadratic Optimization algorithm.

Protein Structure, Family, & Fab Databases The structures deposited in the Protein Data Bank are often problematic to use, because of chronic format errors. CCG has processed all the PDB structures, corrected many common errors and produced a cleaner version of the PDB. Search the database using Code, Header, Compound, Title, HET groups, resolution, etc. The cleaned database is subjected to an exhaustive and iterative structural clustering procedure to generate the Structural Family Database. The result is a database of structural families in excellent agreement with expert hand curated family databases.

Remote Homology & Fold Identification Search the Structural Family Database with a fold detection methodology to identify relevant protein families. The search uses a FastA-type local alignment followed by a family membership test based upon full multiple alignment and Z-score significance testing. Folds of even distantly related homologues can be reliably identified with few false positives (unlike pairwise searches). Run the search in parallel with MOE/smp compute cluster technology to perform timely whole-genome identifications.

Multiple Sequence/Structure Alignment & Analysis Find optimal alignments of protein sequences, given both sequence-only and structural data using CCG's unique technology. The number of protein structures is not limited. Use arbitrary constraints and weightings of secondary structures for the alignments. Simultaneously use sequence and 3D structure information to enhance the quality of the resulting alignment, especially in the problem areas.

Homology Modeling & Macromolecular Simulation Build homology models including multimer models from an amino-acid sequence by assembling fragments of experimentally determined backbone structures from one or more templates, selection of sidechain conformations from a rotamer library, followed by a refinement protocol based on forcefield energy minimization. Specify a loop dictionary for knowledge based loop modeling. The homology models are scored with various scoring functions including MM/GBVI. Include environment units such as bound ligands and conserved waters in the structural template.

Mutation & Rotamer Exploration Discover accessible amino acid side chain conformations with MOE's Rotamer Explorer. Predicts the structure of amino acid mutations in a 3D protein structure and candidate rotamers using an energy-based scoring function and visually analyze them using MOE's graphical interface.

Protein Geometry Quality Assessment Assess the reliability of predicted structures with statistical measures of quality derived from X-ray crystallographic data. Interactive visualization plots such as Ramachandran plots, rotamer strain energy, solvation energy, non-bonded atom clashes and backbone geometry can be used in combination with raw data tables for detailed geometric analysis to identify and isolate regions of predicted structures that require further treatment. Export textual reports and graphics to image files.