Meiler Lab

Protein de-novo Folding

Methods Development
Contact Prediction BCL Align Sequence Alignment and Fold Recognition Sparse EPR Data guided Protein Structure Elucidation Jufo9D Secondary Structure and TM Span Prediction Protein Structure Prediction using Fold Templates BCL::Cluster: Clustering biological molecules with PyMOL visualization Gradient Minimization for Structure Refinement RosettaTMH
Applications
Modeling of Protein IIIA Structure Determination of DsbB using Paramagnetic Restraints Structure determination of KCNE3 using paramagnetic restraints

Protein Structure Prediction from Sparse Data

Methods Development
Protein Structure Prediction Cryo-EM Fit Cryo-EM Guided Protein Fold Elucidation Membrane Protein Structure Prediction using Sparse NMR Restraints RosettaEPR BCL::EMFitMinimize Protein Structure Prediction using SAXS Data
Applications
Modeling Rhodopsin Interaction with G-Protein and Arrestin Mechanism of Activation of the heterotrimeric G protein alpha subunit

Cheminformatics

Methods Development
Chemical Shift Prediction PharmMap Method Development for QSAR Ligand-based Virtual Screening Development of RosettaQSAR Knowledge-Based Small Molecule Conformational Sampling Novel HTS Datasets composed to benchmark ligand-based QSAR Modeling
Applications
mGluR5 Related Neurological Diseases Allosteric Modulators of Neuropeptide Y Receptors Malaria - Inhibition of beta-Hematin Crystallization in Plasmodium falciparum Rapid in silico target identification for anti-malarials

Protein-Protein Interactions

Applications
Structural Characterization of HoxA11 HIV Antibody/Antigens Interactions Antibiotics- Protein/Peptide Interfaces Antibody/Antigens Interaction

Ligand Docking

Methods Development
Rosetta Drug Design Rosetta Design Modeling Partial Covalent Interactions in Protein Ligand Interfaces RosettaLigandEnsemble Drug Design through Foldit Video Game
Applications
Structural Determinants of Antidepressant Drugs GPCR Model Building, Refinement, and Ligand Docking HIV-1 Protease Inhibitor Docking Protein-Ligand Interaction as Cancer Therapeutics

Protein Design

Applications
Evolution of TIM Barrels Chemical Basis of Ligand-Macromolecule Recognition

The Bio Chemical Library (BCL)

The Bio Chemical Library (BCL) is a software package that provides unique tools for biological research, such as protein structure determination from sparse experimental data.

The BCL contains the widely used secondary structure prediction program JUFO, a folding algorithm that assembles secondary structure elements, and loop construction tools that complete protein backbones. With this series of protocols the BCL allows construction of backbone models for large and membrane proteins from the primary sequence. Among its unique strengths are the incorporation of sparse and low resolution data into folding simulations.

Additionally, the BCL contains a suite of cheminformatics tools that allow construction of quantitative structure-activity-relation (QSAR) models for virtual screening, pharmacophore mapping, and drug design.

The BCL is comprised of over one thousand classes organized in 38 namespaces with approximately 200,000 lines of code that form a collection of C++ algorithms developed since 2005. The BCL and its applications have become popular, with more than 50,000 users of the online servers and more than 200 academic licensees.

A movie showing the evolution of the bcl source and include tree made with Gource

Download video: Flash format | MPEG format

A code swarm video that illustrates individual developer contributions and the expanding diversity of bcl projects and applications. In an academic setting, it is easy for code to become abandoned as students graduate and leave the lab. The ongoing evolution of the bcl speaks to its extensibility and adherence to modular, object-oriented, design.

Download video: Flash format | MPEG format

Current Project Members: Jens Meiler
Alumni Project Members: Mert Karakas , Ralf Mueller , Rene Staritzbichler , Nils Woetzel , Mariusz Butkiewicz , Steffen Lindert , Sten Heinze , Nathan Alexander , Edward W. Lowe Jr , Pedro Teixeira , Brian Weiner , Gregory Sliwoski , Jeff Mendenhall , Sandeep Kothiwale , Dan Viox , Daniel Putnam

Center for Structural Biology
465 21st Ave South, BIOSCI/MRBIII
Vanderbilt University, Nashville, TN