Journal Articles

Assessment of fully automated antibody homology modeling protocols in molecular operating environmentAssessment of fully automated antibody homology modeling protocols in molecular operating environmentJohannes K. X. Maier and Paul Labute
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
Wiley Open Access
   

A Cavity Corrected 3D-RISM Functional for Accurate Solvation Free EnergiesA Cavity Corrected 3D-RISM Functional for Accurate Solvation Free EnergiesJean-François Truchon, B. Montgomery Pettitt, and Paul Labute
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
ACS AuthorChoice: Free Access
   

Identifying Structural Domains of Proteins Using ClusteringIdentifying Structural Domains of Proteins Using ClusteringHoward J Feldman
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
BioMed Central Open Access
   

Variability in Docking Success Rates Due to Dataset PreparationVariability in Docking Success Rates Due to Dataset PreparationC. R. Corbeil, C. I. Williams and P. Labute
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
Springer Open Access
   

Scaffold Replacement in MOEScaffold Replacement in MOES. Grimshaw
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.
   

Training a Scoring Function for the Alignment of Small MoleculesTraining a Scoring Function for the Alignment of Small MoleculesS. L. Chan and P. Labute
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
ACS AuthorChoice: Free Access
   

Calibrative approaches to protein solubility modeling of a mutant series using physicochemical descriptorsCalibrative approaches to protein solubility modeling of a mutant series using physicochemical descriptorsW. F. Long and P. Labute
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
Springer Open Access
   

Pocket Similarity: Are α Carbons Enough?Pocket Similarity: Are α Carbons Enough?H. J. Feldman and P. Labute
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
ACS AuthorChoice: Free Access
   

LowModeMD—Implicit Low-Mode Velocity Filtering Applied to Conformational Search of Macrocycles and Protein LoopsLowModeMD—Implicit Low-Mode Velocity Filtering Applied to Conformational Search of Macrocycles and Protein LoopsP. Labute
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
ACS AuthorChoice: Free Access
   

SD File Processing with MOE Pipeline ToolsSD File Processing with MOE Pipeline ToolsA. M. Clark and P. Labute
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.
   

Ligand Scaffold Replacement using MOE Pharmacophore ToolsLigand Scaffold Replacement using MOE Pharmacophore ToolsA. Deschênes and E. Sourial
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: Assignment of Macromolecular Protonation State and GeometryProtonate 3D: Assignment of Macromolecular Protonation State and GeometryP. Labute
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.
   

Ligand Interaction DiagramsLigand Interaction DiagramsA. M. Clark
2D active site diagrams showing the ligand, nearby residues and various types of interactions.
   

Active Site Visualization and AnalysisActive Site Visualization and AnalysisP. Labute
An Integrated Application in MOE for the Visualization and Analysis of Protein Active Sites with Molecular Surfaces, Contact Statistics and Electrostatic Maps.
   

2D Structure Depiction2D Structure DepictionA. M. Clark
Structure diagrams can be generated from molecular connection tables in MOE.
   

Molecular Orbitals in MOEMolecular Orbitals in MOEA. M. Clark
New functionality in MOE for plotting molecular orbitals generated from MOPAC wavefunctions.
   

Relational Database Access in MOERelational Database Access in MOES. Burlington
An overview of the JDBC model used in MOE for connecting to and manipulating relational databases.