Computational Chemical and Structural Biology
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.
Chemistry summer student Don Davis was awarded a Warren Fellowship for this summer. Congratulations, Don!
The grant typically supports students for 2 years. Congraulations, Michaela!
Cristina was a visiting student in the Meiler lab. Congratulations, Crisitina!
Congratulations to Mariusz, Liz, Sten, and Elizabeth!
Congratulations, Dr. DeLuca!
Jeff and Bian presented on "Prediction of KCNQ1 Mutations Associated with Long-QT Syndrome." Congratulations!!
Elizabeth's undergraduate honors thesis was entitled " Structural Studies on Growth Hormone Secretagogue 1a and Ghrelin Interactions." Congratulations, Elizabeth!
Jonas was competing in the 0-9 age group. Congratulations, Jonas!!
Meiler laboratory graduate accepted a 2-year lecturer position at Rollins College in Orlando, Florida. Congratulations, Kelli!
The fellowship includes a 3-year stipend. Congratulations, Alex!
Meiler laboratory graduate accepted an assistant professorship position in the Chemistry Department at The Ohio State University in Columbus, Ohio. Congratulations, Steffen!
Great job, Brittany! See the post here: http://nationalsciencefoundation.tumblr.com/post/112625916214/inspired-by-role-models
Rocco Moretti presented workshop materials to 60 participants!
The meeting took place on March 4-8 at Lake Tahoe and had 160 participants
Sten Heinze successfully defended his dissertation entitled "Improvements for BCL::Fold de novo protein structure prediction".
Dr. Meiler was one of fifteen faculty members selected for the Chancellor Faculty Fellows Program. This competitive program recognizes and supports outstanding young scholars from a diverse set of disciplines across Vanderbilt's campus. (http://www.vanderbilt.edu/provost/initiatives/chancellors-fellows-program/) Congratulations, Jens!
Alyssa passed phase II of her qualifying exam in the Neuroscience department. Congratulations!
Alex received this award for his poster presentation at the ACS meeting in San Francisco. Congratulations, Alex!
Stephanie Hirst DeLuca successfully defended her dissertation entitled "Protein Structure Elucidation by Combining Computational and Experimental Methods"
Published in JBC! Read all about it here: http://www.jbc.org/content/early/2014/07/18/jbc.M114.572875
Darwin Fu won an informatics graduate student fellowship from the Phrma foundation. Congratulations, Darwin!
The Meiler Laboratory is one of several laboratories that have been awarded a University Central Discovery Grant for the proposal entitled "An Intel Xeon Phi Coprocessor (IXP-CPU) Computing Cluster for ACCRE". Congratulations!
The Ligand Docking ROSIE app is now available! Please visit: http://rosie.rosettacommons.org/ligand_docking
Mariusz Butkiewicz successfully defended his dissertation entitled: Advancing Quantitative Structure Activity Relationship Strategies in ligand-based Computer-Aided Drug Design.
Jordan Willis successfully defended his dissertation entitled: Rational Antibody Design: From Mechanisms of Binding to Novel Vaccine Strategies.
Yan constructed a full length model of Metabotropic Glutamate Receptor 1 and docked a focused library of ligands according to their Structure-Activity Relation.
Whether you are a Rosetta newcomer or an advanced user, you are invited to take part in our 2014 Rosetta workshop, April 28 - May 1, to learn how Rosetta can be used for protein modeling, with an emphasis of membrane proteins. Details and Registration Information Tutorials from the 2011 workshop
After learning about using Rosetta to model membrane proteins, stick around to learn more about them at the Vanderbilt Center for Structural Biology conference entitled Biomolecular Structure, Dynamics, and Function: Membrane Proteins!
The Vanderbilt Center for Structural Biology is hosting the Biomolecular Structure, Dynamics, and Function: Membrane Proteins Symposium from May 2-4, 2014. The Early Registration deadline is March 1, 2014! Details and Registration Information
The BioChemical Library (BCL) version 3.1 is now released for Linux, Windows, and Apple and is available for download on meilerlab.org. This release features a new single user academic license, which is now distributed via a webserver on the meilerlab.org website. The new licensing systems enables users at academic and other non-profit institutions to receive a license file within seconds, along with an email detailing how to use it and install the BCL.
This release also includes a number of bug fixes and enhancements, as well as a new application (protein:FusionProtein) for working with chimeric proteins. Brief summaries of all released BCL applications are available on the bclcommons webpage.
Friends and collaborators outside the lab can download the newest release from meilerlab.org and use it with a license file obtained from http://www.meilerlab.org/servers/bcl-academic-license
Congratulations to Daniel!
The VICB award recognizes high-impact research by Vanderbilt researchers. This publication is one of only 6 in the department with a sufficiently high impact (45 citations in total) for the 2014 awards.
Congrats Yan and Jessica!
Dr. Edward W. Lowe, Jr. received a second high performance GPU hardware award from NVIDIA for his work in accelerating algorithms important in biology and chemistry using multiple GPUs. Congrats Will!
Steven McIntyre, an undergraduate student advised by Axel Fischer in the Meiler laboratory, was selected as one of the first recipients of the Littlejohn fellowship. The fellowship encourages undergraduates to participate in research and scholarship across the humanities, natural sciences, and social sciences. Congats Steven!
Drs. Annette Beck-Sickinger and Torsten Schoeneberg from Leipzig University and Jens Meiler from Vanderbilt University receive a grant "Ensemble Docking Interrogates Structural Determinants of Ligand-Protein Interactions" that is jointly funded by the National Science Foundation (NSF) and the Deutsche Forschungsgemeinschaft (DFG). The grant will develop a novel docking algorithm that leverages Structure-Activity-Relations (SAR) and apply this algorithm to understand regulation of G-Protein Coupled Receptors (GPCRs).
Steven Combs successfully defended his dissertation entitled "Identification and Scoring of Partial Covalent Interactions in Proteins and Protein Ligand Complexes." Congrats Steven!
The BioChemical Library version 3.0 is available for download on meilerlab.org. This release features our suite of cheminformatics and QSAR applications, along with new and improved extensions to bioinformatics applications, including JUFO9D, membrane-folding protocols, and SAXS simulation.
User-interface improvements include a friendlier command line interface that offers suggestions whenever options are mistyped, and earier to read help dialogues (and many more of them!),
Download the newest release from the bcl downloads page.
Stephanie is one of only 30 recipients of this year's National Federation of the Blind Fellowship, for which there were over 700 applicants. Congratulations Stephanie!
Tyler Gilcrest, a VU undergraduate researcher in the Meiler Lab, graduated with honors from the Vanderbilt chemistry program. Tyler's performance earned him the Thomas W. Martin award for excelling in physical chemistry. Excellent job Tyler!
The 3 Minute Thesis competition sponsored by the Vanderbilt Graduate Student Council challenged graduate students in all fields across campus to present their thesis in only 3 minutes to a diverse audience. Students were challenged to present their research topic, explain how the research is conducted, and identify what impact it will have on the general or academic community. Elizabeth Nguyen, a graduate student in the Meiler Lab, received a co-first place prize for her presentation on "Progress Towards Unlocking the Treatment for Cognitive Impairment". Her research involves the computational modeling of G-protein coupled receptors, specifically metabatropic glutamate receptor 5 and its binding site for drugs used to treat schizophrenia and Fragile X Syndrome.
Amanda's stipend will allow her to explore computational design of membrane protein ligand interactions. Congratulations to Amanda!
Stephanie will be giving a talk on RosettaEPR at the 2013 Biophysics conference in South Korea, May 22, at 10:15-10:30 AM
The Meiler lab receives an ORAU/ORNL High Performance Computing (HPC) Grant: "Investigation of the Mechanism of Cellulose Synthesis in Plants Using Neutron Scattering and High Performance Computing"
Dr. Lemmon received a fellowship from Emerging Leaders in Biosecurity Initiative to facilitate meeting with leaders in Biosecurity.
Whether you are a Rosetta newcomer or an advanced user, you are invited to take part in our 2012 Rosetta workshop, Nov 13-16, to learn how Rosetta can be used for protein structure prediction. Details and Registration Information Tutorials from the 2011 workshop
Faculty of 1000, a large group of researchers in the fields of biology and medicine that identify the most relevant research in the field, has recommend EM-fold: de novo atomic-detail protein structure determination from medium-resolution density maps., Structure, 2012
The BCL CASP team (Sten Heinze, Daniel Putnam, and Pedro Teixeira) have been awarded an attendance fellowship to defray the costs of attending the CASP conference. Congrats to the BCL CASP team!
Dr. Edward W. Lowe, Jr. received a high performance GPU hardware donation from NVIDIA for his work in accelerating algorithms important in biology and chemistry. Congrats Will!
The annual Vanderbilt Institute for Chemical Biology proved especially rewarding this year, with two winners from Meiler Lab. Daniel Putnam won an Ipad through a raffle. Mariusz Butkiewicz co-authored a poster together with Rebecca Sandlin from the David Wright laboratory "Finding the Pathway: New Machine Learning Paradigms for the Identification of Lead Compound Targets from Phenotypic Antimalarial Assays" that won a poster prize. Congratulations!
The Meiler lab was awarded a grant "Computational Design of Protein-Ligand Interfaces - a Therapeutic Strategy" from the NIH National Institute of General Medical Sciences (NIGMS). The grant will create advanced methodology to computationally design and experimentally verify protein-ligand interfaces. It will further explore use of these methods to create protein therapeutics for treatment of prostate cancer, bacterial infection, and cocaine overdosing.
Gordon Lemmon, Steven Combs, Jordan Willis, and Sam DeLuca presented research talks at the Rosetta conference. The topics include: "Refactoring Rosetta for Chemistry", " Knowledge-Based Potentials for Partial Covalent Interactions", "Anti-HIV antibody design using Rosetta", and "RosettaQSAR - protein-ligand docking guided by pharmacophore maps"
The Meiler laboratory was awarded a grant "Ligand-Macromolecule Recognition: A Collaboration in Research and Education Between Vanderbilt and Leipzig University" from the NSF Office of International Science and Engineering (OISE). It is the objective of this proposal to develop a sustainable collaboration in education and research between Vanderbilt and Leipzig Universities in the area of chemical biology.
Congrats to Steffen, who received a postdoctoral fellowship from the American Heart Association
Dr. Nathan Alexander successfully defended his dissertation: Protein structure elucidation from computational techniques and sparse EPR data
Daniel's research will be on the topic of Small Angle X-ray Scattering (SAXS) Restraints to Promote de Novo Protein Structure Prediction
Dr. Julia Koehler successfully defended her dissertation: Method development for membrane protein structure determination using NMR spectroscopy and computational techniques
The awards provide financial support for presenting their research at the Computational Biophysics to Systems Biology (CBSB12) symposium.
Stephanie Hirst receives the prestigious Ruth L. Kirschstein National Research Service Award (NRSA) from NIH for her project "Investigating the Role of Substrate Binding in LeuT Transport With RosettaEPR." Congrats Stephanie!
The Meiler laboratory receives a Research Experiences for Undergraduates (REU) grant from NSF for research related to the CAREER award: "Cryo-EM guided de novo Protein Fold Elucidation"
The Meiler laboratory receives a pilot project grant from the Vanderbilt Diabetes Research and Training Center (DRTC) "Exploring Allosteric Modulators of Neuropeptide Y4 Receptor"
Brittany presented her research plan entitled "Computational Design of Protein-Ligand Interfaces in (beta/alpha)8 Barrels for Applications in Protein Therapeutics"
Jordan Willis was invited to give an oral presentation at the Keystone Symposia on HIV Vaccines
Brittany Allison, a chemistry student in the Meiler laboratory, received a prestigious National Science Foundation (NSF) Graduate Research Fellowship. Brittany works on computationally engineering proteins that bind small molecules. Her research has implications for understanding the fundamentals of protein-ligand interaction, engineering enzymes, and protein therapeutics. Brittany will start her fellowship after completing her training on the Chemical Biology Training Program, an NIH-funded initiative of Vanderbilt's Institute for Chemical Biology and the Chemistry Department.
Sandeep presented his research plan entitled "Enhancement of drug discovery tools through knowledge based conformational sampling and chemical shift predictions"
Daniel Putnam's AMIA paper - "Exploring Schizophrenia Drug-Gene Interactions Through Molecular Network and Pathway Modeling", has been accepted as one of the eight finalists in the Student Paper Competition at the American Medical Informatics Association conference in October. Update 10/28/2011: Daniel was awarded 2nd place at the conference, congratulations, Daniel!
Nils Woetzel successfully defended his thesis, “A novel approach to de novo protein structure prediction using knowledge based energy functions and experimental restraints."
Zollie White, an undergrad from Morehouse College, spent the summer of 2011 researching with Will Lowe in the Meiler Lab through the Vanderbilt REU program. He presented this research at the 2011 Herty Medalist Undergraduate Research Symposium held at Morehouse College was awarded the top prize. For this, he received a one-year membership to the American Chemical Society (ACS) and a $500 travel award to a national ACS conference. Congrats, Zollie!
Congrations to Mert Karakas for having successfully defended his thesis "BCL::Fold-De novo Protein Structure Prediction by Assembly of Secondary Structure Elements"
Will Lowe received an NSF fellowship for his project "PROPMAP: A Novel GPU-accelerated Structure-Property Relationship Mapping Algorithm Utilizing Volunteer Computing." The prestigious award supports Dr. Lowe's research for three years in the Meiler Lab. Congrats, Will!
Liz Dong of the Jens Meiler lab at Vanderbilt recently received a short term research grant to study at the Univeristy of Leipzig in Leipzig, Germany. She will spend one month this fall developing a computational method that will allow for the binding pose of a drug within a receptor to be determined. Her method will be guided by experimental data collected on drugs that bind G-protein coupled receptors, working with the lab of Torsten Schöneberg. Congrats, Liz!
Mariusz passed his qualifying exam with his proposal: Comprehensive protein-ligand interaction mapping through quantitative structure activity relationships. Congratulations Mariusz!
Kelli's was awarded an NIH NRSA doctoral fellowship to investigate "Conformational Changes Underlying Intracellular Gating of the Leucine
Transporter." Congratulations Kelli!
Sten passed his qualifying exam with his proposal: A novel approach
to de novo protein structure prediction using multiple partial templates. Congratulations Sten!
Ralf successfully defended his thesis, Machine Learning Algorithms for Prediction of Biological Activity and Chemical Properties, earning his PhD, Congratulations Ralf!
Dr. Jens Meiler was promoted to Associate Professor with tenure.
Congratulations to Andrew Morin on successfully defending his PhD thesis on April 26, 2011. The thesis was presented on "The Computaional Design of Protein Ligand Interfaces".
Steven Combs has successfully passed his qualifying exam on April 23, 2011 and proposed his research on "Thermostabilization of industrially relevant proteins through computational design of partial covalent interactions".
Meiler Laboratory has been awarded Vanderbilt University Discovery Grant for research on "De novo Design of Large protein".
Liz Dong has won best oral presentation prize at Chemical & Physical Biology retreat at Nashville Zoo on April 18, 2011. She gave her oral presentation on "Structural studies of the interaction between mDlu5 and allosteric modulator". Congratulations to Liz !!!
Julia Koehler won a travel grant to attend the Gordon Research Conference "Computational Aspects - Biomolecular NMR" in May 2011 and will present her work on " De novo membrane protein folding from sparse NMR data ". Congratulations!!!
Brittany Allison, a graduate student at Meiler Lab has successfully passed her Priliminary Qualification Exam on April 6, 2011.
Louesa Akin is a undergraduate student attending Centre College in Kentucky who pursues research in the Meiler laboratory focused on Membrane Protein Structure Prediction using sparse NMR restraints. She was selected to receive the Goldwater Scholarship for undergraduate students. Louesa participated in the Summer Science Academy program in summer 2010 and will participate in the Research Experience for Undergraduates in chemical biology in summer 2011.
Liz Dong is a MD/PhD student in the second year of her graduate studies. She won the prestigious PhRMA-Paul Calabresi Medical Student Research Fellowship. The fellowship is offered to medical students who have substantial interests in research and teaching careers in pharmacology - clinical pharmacology. Liz works on new technologies in the Meiler laboratory to develop allosteric modulators of metabotropic glutamate receptors, important targets for many neurological diseases.
David Nannemann will be defending his Doctoral research on "Directed Biosynthesis of the Nucleoside Analog Drug Didanosine", at the Stevenson Center, Room 5502, 2:00 pm.
Stephanie Hirst unconditionally passed her Qualifying Exam on February 3, 2011 and the proposal was called "Structural Elucidation of the Role of Na+ and Leucine Binding in the LeuT Transport Mechanism using ROSETTAEPR". Congratulations to Stephanie!!!
Steffen presented his doctoral research dissertation “CryoEM guided de-novo protein folding” on November 22nd, 2010. His thesis committee approved his presentation and accepted his research, making him the first to complete the Chemical and Physical Biology PhD Program. Congratulations, Steffen!!
Steffen Lindert will give a presentation at the Pacific Symposium on Biocomputing in January on Hawaii (about EM-Fold and our results participating in the cryoEM modeling challenge). He received an NIH travel award to cover the costs associated with the conference.
Congratulations to Liz Dong, an MD/PhD student in the Meiler lab, on her successful completion of qualifying exams on 9/2/2010
Congratulations to Meiler Lab members Kristian W. Kaufmann, Gordon H. Lemmon, Samuel L. DeLuca, and CSB outreach coordinator, Jonathan H. Sheehan! Their recent publication, "Practically Useful: What the Rosetta Protein Modeling Suite Can Do for You" made the list of the TOP 20 most downloaded articles from the journal Biochemistry.