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Lauren Porter, PhD

About

Picture of Lauren Porter, PhD

Lauren Porter, PhD

Stadtman Tenure Track Investigator, NLM DIR

Dr. Porter’s lab researches fold-switching proteins, a recently discovered class of proteins that can change their structures and functions in response to changes in their environments.

Contact Information

Building 38A, 8600 Rockville Pike, Bethesda, MD 20894

Tel: 301-827-0924

lauren.porter@nih.gov

Research Interests

No introductory-level biochemistry textbook is complete without a chapter about how a protein’s primary sequence of amino acids determines its fold. Despite much technical progress, however, solving protein structures experimentally remains very laborious and expensive, and knowing the structures of diverse proteins is crucial for both basic research and drug design. Thus, computational prediction of a protein’s structure from its amino acid sequence is a challenge of major importance.

Nearly all computational work so far has focused on predicting a single protein structure from the protein’s amino acid sequence. Dr. Porter’s research challenges the one-sequence-one-structure paradigm. In a recent publication, Loren Looger and she found nearly 100 examples of proteins that can adopt more than one stable fold. This structural heterogeneity allows proteins either to perform more than one function or to be highly regulated in cells. Through the NLM Division of Intramural Research, her lab is developing data-driven computational approaches to predict which amino acid sequences can switch folds. She and her lab members validate these predictions experimentally at the National Heart, Lung, and Blood Institute (NHLBI).

This basic research has significant implications for human health. A number of fold-switching proteins are associated with diseases such as cancer, autoimmune disorders, and bacterial and viral infections. Right now, very little is known about how these proteins work. Understanding their mechanisms could lead to development of new therapeutics.

Biography

Dr. Lauren Porter is a Stadtman Tenure-track Investigator with a primary appointment at NLM and a secondary appointment at NHLBI. Prior to coming to the NIH, Dr. Porter spent 7 years studying the biological and biophysical properties of fold-switching proteins, first at the University of Maryland and then at the Howard Hughes Medical Institute, Janelia Research Campus. She is the corresponding author of several recent papers reporting the results of this research. One of them, published in PNAS, was highlighted by two members of Faculty of 1000. For her research on protein fold switching, Dr. Porter has received the Maryland Academy of Science’s Outstanding Young Scientist Award (2015) and a National Research Service Award (2014), and she has presented her research at nearly 20 national and international conferences.

Publications

Chakravarty D, Schafer JW, Chen EA, Thole JF, Ronish LA, Lee M, Porter LL. AlphaFold predictions of fold-switched conformations are driven by structure memorization. Nat Commun. 2024 Aug 24;15(1):7296. doi: 10.1038/s41467-024-51801-z. PubMed PMID: 39181864; PubMed Central PMCID: PMC11344769.

Porter LL, Artsimovitch I, Ramírez-Sarmiento CA. Metamorphic proteins and how to find them. Curr Opin Struct Biol. 2024 Jun;86:102807. doi: 10.1016/j.sbi.2024.102807. Epub 2024 Mar 26. Review. PubMed PMID: 38537533; PubMed Central PMCID: PMC11102287.

Schafer JW, Chakravarty D, Chen EA, Porter LL. Sequence clustering confounds AlphaFold2. bioRxiv. 2024 Jan 9;. doi: 10.1101/2024.01.05.574434. PubMed PMID: 38313252; PubMed Central PMCID: PMC10836070.

Chen EA, Porter LL. SSDraw: Software for generating comparative protein secondary structure diagrams. Protein Sci. 2023 Dec;32(12):e4836. doi: 10.1002/pro.4836. PubMed PMID: 37953705; PubMed Central PMCID: PMC10680343.

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