We present a method for automatic modeling of the FV region of an immunoglobulin based upon the use of a precompiled antibody x-ray structure database, which serves as a source of framework and hypervariable region structural templates that are grafted together. We applied this method (on common desktop hardware) to the Second Antibody Modeling Assessment (AMA-II) target structures as well as an experimental specialized CDR-H3 loop modeling method. The results of the computational structure predictions will be presented and discussed.
Proteins, 2014 82: 1599–1610. doi:10.1002/prot.24576
We show that an Ng bridge function modified version of the three-dimensional reference interaction site model (3D-RISM-NgB) solvation free energy method can accurately predict the hydration free energy (HFE) of a set of 504 organic molecules.
J. Chem. Theory Comput., 2014 (Article ASAP), doi:10.1021/ct4009359
This study presents a novel clustering-based approach to domain identification, which works equally well on individual chains or entire complexes. The method is competitive with others, achieving 70% agreement with SCOP on a large non-redundant data set, and 80% on a set more heavily weighted in multi-domain proteins on which both SCOP and CATH agree.
BMC Bioinformatics, 2012, 13:286 doi:10.1186/1471-2105-13-286
The MOE software with the newly developed GBVI/WSA dG scoring function is used throughout the study. For 80 % of the Astex targets, the MOE docker produces a top-scoring pose within 2 Å of the X-ray structure. For 91 % of the targets a pose within 2 Å of the X-ray structure is produced in the top 30 poses.
J Comput Aided Mol Des, 2012, 26 (6), pp 775-786
A new application for performing scaffold replacements, fragment linking, and R-group optimization is presented. The application is applied to the discovery of novel p38 MAP kinase inhibitors, using the structures of a screening hit and the mature BIRB-796 inhibitor as starting points.
A comprehensive data set of aligned ligands with highly similar binding pockets from the Protein Data Bank has been built. Based on this data set, a scoring function for recognizing good alignment poses for small molecules has been developed.
J Chem Inf Model, 2010, 50 (9), pp 1724-1735
A set of physicochemical properties describing a protein of known structure is employed for a calibrative approach to protein solubility.
J Comput Aided Mol Des, 2010, 24 (11), pp 907-916
A novel method for measuring protein pocket similarity was devised, using only the α carbon positions of the pocket residues.
J Chem Inf Model, 2010, 50 (8), pp 1466-1475
We present a method for conformational search of complex molecular systems such as macrocycles and protein loops.
J Chem Inf Model, 2010, 50 (5), pp 792-800
We present a series of SD command line tools for the preparation of small molecule databases including protonation and tautomer enumeration, filtering, sorting and descriptor calculations.
We describe a scaffold replacement methodology based upon an extension of MOE's pharmacophore features. The special "Link" pharmacophore features can be used in conjunction with other features, SMARTS patterns and volume constraints.
Protonate 3D is an application which assigns protonation states and geometries (taking titration into account) to macromolecular structures using an algorithm that solves the Unary Quadratic Optimization problem.
2D active site diagrams showing the ligand, nearby residues and various types of interactions.
An Integrated Application in MOE for the Visualization and Analysis of Protein Active Sites with Molecular Surfaces, Contact Statistics and Electrostatic Maps.
Structure diagrams can be generated from molecular connection tables in MOE.
New functionality in MOE for plotting molecular orbitals generated from MOPAC wavefunctions.
An overview of the JDBC model used in MOE for connecting to and manipulating relational databases.