Marco Mravic, PhD
Assistant Professor
Department of Integrative Structural and Computational Biology
Research Focus
Mravic lab uses protein design and integrative computational approaches to challenge our understanding of biomolecular structure, function, and physical chemistry - mainly within the cellular membrane environment.
The three focus areas of our group are
(1) Designing of small synthetic membrane proteins as simple model systems to test fundamental biophysical questions governing molecular structure and function.
(2) De novo design and high-throughput engineering of custom chemical biology tools targeting membrane proteins directly at their lipid-embedded regions to probe molecular mechanism and therapeutic opportunities.
(3) Molecular modeling and dynamics simulations that integrate diverse experimental data to better understand critical molecular events at cellular membranes
Our lab's mission is to take an engineering approach (with new tool molecules or custom model systems) to investigating important biophysical principles underlying protein structure and activity in lipid as well as molecular determinants of disease. Our protein design efforts aim to engineer and study simplified model systems or novel chemical tools that allow us to proactively hypothesize, test, and establish chemical 'rules' for structure and function within the distinct environment of cellular membranes. These rules emerge through integrating cellular and biophysical experiments with bioinformatics, machine learning, all-atom simulations, and theoretical energy calculations. The lab's experimental expertise to interrogate membrane protein structure and function are highly multi-disciplinary, ranging from total protein chemical synthesis, structural biology (X-ray, NMR, cryo-EM), cell-based assays, and in vitro biophysics.
Select Publications
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Golden, Kiana; Avarvarei, Catalina; Anderson, Charlie T.; Holcomb, Matthew; Tang, Weiyi; Dai, Xiaoping; Zhang, Minghao; Mailie, Colleen A.; Sanchez, Brittany B.; Chen, Jason S.; Forli, Stefano; Mravic, Marco Design principles of the common Gly-X6-Gly membrane protein building block. Proceedings of the National Academy of Sciences of the United States of America 2025, 122.
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Maillie, Colleen A.; Zhang, Minghao; Gosiet, Nadia; Goldenfeld, George; Ward, Andrew B.; Mravic, Marco Programmed inhibition of an innate immune receptor via de novo designed transmembrane proteins. bioRxiv 2025, 2025.05.31.657109.
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Mravic, Marco; He, Li; Kratochvil, Huong T.; Hu, Hailin; Nick, Sarah E.; Bai, Weiya; Edwards, Anne; Jo, Hyunil; Wu, Yibing; DiMaio, Daniel; DeGrado, William F. De novo-designed transmembrane proteins bind and regulate a cytokine receptor. 2024, 20, 751-760.
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Maillie, Colleen A.; Golden, Kiana; Wilson, Ian A.; Ward, Andrew B.; Mravic, Marco Ab initio prediction of specific phospholipid complexes and membrane association of HIV-1 MPER antibodies by multi-scale simulations. 2025, 12.
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Mravic, Marco; Thomaston, Jessica L.; Tucker, Maxwell; Solomon, Paige E.; Liu, Lijun; Degrado, William F. Packing of apolar side chains enables accurate design of highly stable membrane proteins.. Science 2019, 363, 1418-1423.
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Tang, Weiyi; Jojoa-Cruz, Sebastian; Li, Jiayi; Goldenfeld, George; Mravic, Marco MemPPI platform for measuring and engineering membrane protein-protein interactions in mammalian cells via split nanoluciferase. 2026, 35, e70496.
