Meiler Lab 2018 Meiler Lab 2018
picture 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 more...
picture Protein Structure Prediction
Despite improvements on both experimental techniques and computational prediction methods for small and medium sized proteins, structure elucidation and prediction for larger proteins remains a major challenge. We are developing a structure prediction algorithm that incorporates data of various experimental techniques but also to be used as a standalone tool. The algorithm utilizes a novel sampling technique and employs the flexible combination of empirical and experimental scores.The pro more...
picture Fitting molecules in low resolution electron density maps

A growing technique in protein structure determination is cryo-electron microscopy. Cryo-EM provides low resolution electron density maps ( ~8 Ångström) . As this data become more accurate and you can use this data not only to determine the overall structure of protein complexes, but also to determine secondary structure elements and their assembly in the tertiary structure of a protein. The successful field of ab initio protein structure prediction ca more...
picture Antibody/Antigens Interactions
Antibody structural repertoires are determined through diversity of gene segment usage and the introduction of somatic mutations. This structural diversity is responsible for the recognition of an unlimited number of antigens. Traditional techniques for determining structure cannot characterize the breath of structural diversity that these antibody-antigen interactions can adopt because of limited throughput. Using the knowledge-based structural biology program Rosetta, we can use the results from c more...
picture Membrane Protein Structure Prediction using sparse NMR restraints
About 30% of the proteins in the human body are membrane proteins. They have a wide variety of functions within the cell and it is therefore not surprising that over half of all known drugs target them. However, less than 1% of the structures deposited in the ProteinDataBank belong to membrane proteins. The reason for this discrepancy is the difficulty to crystallize them. Also conventional liquid-state NMR techniques reach their limits for membrane proteins more...
picture BCL::Jufo: Simultaneous Prediction of Protein Secondary Structure and Trans-Membrane Spans
A first step towards protein tertiary structure prediction is the identification of secondary structure elements from the sequence. In addition, the identification of trans-membrane spans is required for membrane proteins.

The aim of this project is to simultaneously predict secondary structure and trans-membrane spans with a single tool. The rationale for this approach is the hypothesis that both phenomena are interrelated: more...
picture Rosetta Drug Design
Small molecule design consists of assembly, docking, and scoring. Since Rosetta already has a docking algorithm (RosettaLigand) and a scoring framework, all that is needed for small molecule design is an assembly algorithm. As an initial approach, we have chosen random assembly of fragments from an input library. The algorithm is represented in figure 1. Each cycle of design consists of extending the small molecule with random fragments chosen from a library, filtering small molecule designs based on energ more...
picture High resolution contact prediction
Learning systems have a long history in being applied to reduce the search space for protein structure prediction e.g. artificial neural networks (ANN) and hidden markov models (HMM) are used for protein secondary structure prediction and motif recognition. Recently, ANNs were successfully utilized to derive a consensus amino acid contact prediction for unknown folds from fold recognition techniques. These predictions drive de novo prediction of protein tertiary structure towards better r more...
picture EPR guided protein structure prediction using the BCL
Electron paramagnetic resonance (EPR) can provide structural information on proteins not easily studied by other biophysical techniques such as nuclear magnetic resonance and X-ray crystallography. Inter-residue distances of up to 60Å and residue specific solvent exposure can be measured. Such data can be critical to defining the topology of a protein. However, the amount of information obtained from an EPR dataset is limited by its sparseness and difficulty in r more...
picture Cryo-EM guided de novo Protein Fold Elucidation
Using cryo-electron microscopy (cryoEM) numerous sub-nanometer resolution density maps of large macromolecular assemblies have been recently reported. Although no atomic detail is generally resolved in these density maps, at 7 Å resolution α-helices are observed as density rods. The Primary goal of this project is the development of a computational protein structure prediction algorithm that incorporates the experimental cryoEM density map as restraints. The placemen more...
picture HIV-1 Protease Inhibitor Docking
HIV protease inhibitors (PIs) have been an important and successful model for structure-assisted drug design. At least ten PIs have been approved by the FDA since 1995. However because of HIV-1’s high mutation rate, PI therapies often succumb to drug resistance mutations. Computational methods that predict how a putative inhibitor will interact with various strains of HIV-1 protease will speed the development of new inhibitors that avoid resistance mutation. HIV-1 protease mutants more...
picture TIM Barrel Design
Six of the ten most frequent protein topologies have symmetry on the fold level. We postulate that the evolutionary origin of these symmetric superfolds lies in naturally occurring homo-oligomeric protein complexes that undergo gene duplication and fusion. To test this hypothesis the Rosetta protein design package was used to computationally design a two-fold symmetric variant of imidazole glycerol phosphate synthase (HisF). The new protein, termed FLR, adopts the symmetric βα TIM-barrel superfo more...

About Meiler Lab

Research in our laboratory seeks to fuse computational and experimental efforts to investigate proteins, the fundamental molecules of biology, and their interactions with small molecule substrates, therapeutics, or probes. We develop computational methods with three major ambitions in mind.

A) To enable protein structure elucidation of membrane proteins the primary target of most therapeutics and large macromolecular complexes such as viruses;
B) Design proteins with novel structure and/or function to explore novel approaches to protein therapeutics and deepen our understanding of protein folding pathways.
C) Understand the relation between chemical structure and biological activity quantitatively in order to design more efficient and more specific drugs.


Crucial for our success is the experimental validation of our computational approaches which we pursue in our laboratory or in collaboration with other scientists.


Current research applications focus on new approaches to a) drug and probe development for neurodegenerative disorders and diseases including Schizophrenia, Alzheimer's, and Parkinson's, b) understanding the structural determinants of antidepressant binding to neurotransmitter transporters, c) cardiac arrhythmia as caused by the complex interplay of potassium channel regulation and drug interactions, d) multidrug resistance in cancer and bacterial cells related to multidrug transporter proteins, and e) structural basis of viral infections and antibody activity.


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Congratulations to Jens Meiler for being elected a 2021 AAAS fellow! 2022-02-10

Jens Meiler has been elected a 2021 fellow by the American Association for the Advancement of Science (AAAS) for his contribution in protein structure prediction and design!

Six other members of the Vanderbilt University community were also awarded fellow, check the full article here: Seven Vanderbilt faculty elected as AAAS fellows in 2021 | News | Vanderbilt University

Eli McDonald received the Dissertation Enhancement Grant from the Graduate Leadership Institute! 2020-12-17

Eli McDonald has been awarded a Russell G. Hamilton Graduate Leadership Institute Dissertation Enhancement Grant! The Graduate Leadership Institute selects each year outstanding PhD Students and provides $2000 for research expenses.
Congratulations Eli!

Taylor Jones received the Biomedical Informatics T15 Training Grant (NIEHS funded) for the year 2020-2021! 2020-05-19

Taylor Jones will join Meiler Lab as a graduate student starting from June 1st 2020! The training grant appointment was offered by the Department of Biomedical Informatics of Vanderbilt University and it is founded by NIEHS.

Congratulations Taylor, and welcome to Meiler Lab!

Tiffany Alyssa Shields received the Merck Index Award! 2020-04-23

The Merck Index Award is awarded annually to an outstanding graduating senior who is going on to medical school or graduate school.

Congratulations Tiffany!

Aodong Liu received the Thomas W. Martin Award! 2020-04-22

The Thomas W. Martin Award was established in 1993 in memory of Thomas W. Martin, professor of chemistry at Vanderbilt from 1957 to 1991.  Presented annually to a graduating chemistry major who has excelled in physical chemistry and plans to attend graduate school in chemistry.

Congratulation Aodong Liu!

Pranav Kodali received the Biochemistry Department Aida Nureddin Outstanding Junior Researcher Award! 2020-04-15

Congratulation Pranav!

Congratulations to Dr. Meiler for his dual professorship position with the University of Leipzig and Vanderbilt University 2020-01-28

Former Meiler laboratory graduate student Bian Li receives AHA fellowship. 2019-12-09

Former Meiler laboratory graduate student Bian Li receives distinguished fellowship from the American Heart association (AHA) for his project "Biophysical Insights into and Probabilistic Interpretation of Cardiac Ion Channel Variants of Uncertain Significance"

Congratulations Bian!

Brennica Marlow has been selected to co-chair a session at the Biophysical Society 64th Annual Meeting 2019-12-09

Brennica Marlow has been selected to co-chair the session “Platform: Protein-Lipid Interactions I” at the Biophysical Society 64th Annual Meeting. This session will take place in San Diego CA on Sunday, February 16, 2020.


Congratulations Nica!

Rocco Moretti, PhD has been promoted to Research Associate Professor 2019-06-17

Rocco Moretti, PhD has been promoted to Research Associate Professor in recognition to his contributions to research excellence at Vanderbilt University, the Department of Chemistry, the RosettaCommons (, and the Meiler laboratory.

Congratulations Rocco!

Marion Sauer wins the 2019 Student Leadership award 2019-06-15

Congratulations Marion and thank you for your community service!

Eli McDonald for receives the Vanderbilt Chemistry Biology Interface Training Grant 2019-05-28

Congratulations Eli McDonald for receiving the Vanderbilt Chemistry Biology Interface Training Grant (NIH-#5T32GM065086) on behalf of the Vanderbilt Institute of Chemical Biology.

Jens Meiler receives Humboldt Foundation award 2018-12-18

Jens Meiler has been selected for the Humboldt Professorship and will now embark on appointment negotiations with the German university that nominated him. If the negotiations succeed, the award will be conferred in May 2019.

More information:

Congratulations Jens!

Shannon Smith receives the PhRMA Foundation Pre-Doctoral Informatics Fellowship 2018-12-11

Shannon Smith receives the PhRMA Foundation Pre-Doctoral Informatics Fellowship.

Congratulations Shannon!

Samuel Schmitz successfully passes his qualification exam! 2018-11-13

Samuel Schmitz successfully passes his qualification exam with the title "A Combined Sequence-Structure Approach to Elucidate Immunome Repertoires".

Congratulations Samuel!

Jessica Finn passed her defense! 2018-11-12

Jessica Finn passed her  defense with the title "Sequence, Structure, and Function Relationships of Human Antibodies"

Congratulations Jessica!

Snyder, B. "'Missing link' may spur new brain disorder drugs" VUMC Reporter March 14, 2014.

Windsor, M., "Vanderbilt, Leipzig research collaboration sees strong results." Research News @ Vanderbilt

Salisbury, D. "Leipzig collaboration yields valuable relationships." Vanderbilt Chemistry 2013.

Bartoo, C. "Controversial info release aids VUMC bird flu research" VUMC Reporter September 6, 2013.

Oak Ridge Associated Universities. "ORAU, ORNL announce winners of high-performance computing grant competition." Oak Ridge Today, 2013.

Snyder, B. "School for Science and Math students shine in Intel competition." VUMC Reporter, Jan 2013.

Meiler, J. "Die Bedeutung des FChO auf deinem akademischen Weg" Faszination Chemie 2013, 66.

Salisburg, D. "The Leipzig Connection," Research News@Vanderbilt, Vanderbilt University, Dec 2012.

Russel, J. "Bigger IS Better", Arts and Science, Vanderbilt University, Spring 2012.

Fortenberry, C. "International Chemistry: Shared reactions from Leipzig to Nashville." Vanderbilt International 2011.

Salisbury, David. "Creation of the largest human-design protein boosts protein engineering efforts." Vanderbilt Reporter, Nov 2011.

Synder, B. "School for Science and Math student sees paper published." VUMC Reporter, Vol XXI, 34. Sep 2011.

Snyder, B. "Study shows how G proteins get "turned on" by receptors" Vanderbilt Reporter 2011.

Baynham, D. Q.; Karakas, M.; Meiler, J. "Protein Structure Prediction Using Rosetta" Young Scientist, May 2011, p11-12

Smith, S. "As Beckman Scholars, undergraduates experience responsibility and research life" Arts & Science, Vanderbilt University, Spring 2011

Schreiber, A.; Meiler, J. "Modellierung G-Protein-gekoppelter Rezeptoren mit ROSETTA " Biospektrum

Joetten, F. "Formvollendet" Bild der Wissenschaft 2010, 4, 18-23.

Omlor, A.; Meiler, J. "Zu Gast im Meiler Lab an der Vanderbilt University in Nashville Tennessee!"

Jaehnigen, S.; Grjasnow, A.; Meiler, J. "Chemische und strukturelle Biologie waehrend eines Praktikum in den USA" Faszination Chemie 2009, 14., p12-16

Marino, M. "Undergraduate Open House" Vanderbilt Reporter 2008, 4.

Lerner, M. "Europe's Brain Drain" European Hospital 2008, 17, 4.

Marino, M. "Program promotes greater diversity in molecular sciences" Vanderbilt Reporter 2007, 3.

Salisbury, D. F. "Campus 'supercomputer' helps decipher mysteries of science" Vanderbilt Register 2

Joetten, F. "Ich, der Roboter" Die Zeit 2007, 41, 42-43.

Meiler, J. "Kuenstliche Intelligenz in Chemie und Biologie" Faszination Chemie 2001, 7, 35-43.

Lukas von Bredow;Lukas von Bredow, Thomas M. Schäfer, Julian Hogenkamp, Maik Tretbar, Daniel Stopper, Fabian K. Kraft, Julian Schliehe-Diecks, Andrea Schöler, Arndt Borkhardt, Sanil Bahitia, Jana Held, Finn K. Hansen
Synthesis, Antiplasmodial, and Antileukemia Activity of Dihydroartemisinin-HDAC Inhubitor Hybrids as Multitarget Drugs (2022) Pharmaceuticals

Maik Tretbar;Reni Kitte*, Sarah Dluczeka, Lorenz Beckmann, Peter Marquardt, Anna Duenkel Andreas Schubert Stephan Fricke, U. Sandy Tretbar *equal first authorship
Chemical and Cytotoxic Activity of three main Sesquiterpenoids from Warburgia ugandensis (2021) Results in Chemistry

Xia Y;Ledwitch K, Kuenze G, Duran A, Li J, Sanders CR, Manning C, Meiler J
A unified structural model of the mammalian translocator protein (TSPO) (2019) J Biomol NMR

Vu O; Mendenhall, Altarawy, Meiler
BCL::Mol2D-a robust atom environment descriptor for QSAR modeling and lead optimization. (2019) J Comput Aided Mol Des.

Brown BP;Mendenhall J, Meiler J
BCL::MolAlign: Three-Dimensional Small Molecule Alignment for Pharmacophore Mapping. (2019) J Chem Inf Model

Roushar FJ;Gruenhagen TC, Penn WD, Li B, Meiler J, Jastrzebska, Schlebach
Contribution of Cotranslational Folding Defects to Membrane Protein Homeostasis. (2019) J Am Chem Soc

Butkiewicz M;Rodriguez AL, Rainey SE, Wieting J, Luscombe VB, Stauffer SR, Lindsley CW, Conn PJ, Meiler J
Identification of Novel Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5 Acting at Site Distinct from 2-Methyl-6-(phenylethynyl)-pyridine Binding. (2019) ACS Chem Neurosci.

Li B;Mendenhall J, Meiler J
Interfaces Between Alpha-helical Integral Membrane Proteins: Characterization, Prediction, and Docking. (2019) Comput Struct Biotechnol J.