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Integrative Structural and Computational Biology

Marco Mravic, PhD

Scripps Fellow
Department of Integrative Structural and Computational Biology
California Campus
Laboratory Website

Scripps Research Joint Appointments

Faculty, Graduate Program

Research Focus

Mravic lab uses protein design and integrative computational approaches to challenge our understanding of biomolecular structure, function, and physical chemistry.

The three focus areas of our group are
(1)  Designing small synthetic membrane proteins as simple model systems to test fundamental biophysical questions governing molecular structure and function.
(2)  De novo design and development of chemical biology tools targeting membrane proteins directly at their lipid-embedded regions to probe disease 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 protein design efforts aim to test and establish chemical ‘rules’ for protien structure and function: rules we hypothesize through merging cellular and biophysical experiments with bioinformatics, all-atom simulations, and theoretical energy calculations.  Our lab's mission is to produce simple model molecules custom-made to investigate important biophysical principles underlying protein structure and activity in lipid as well as identify molecular determinants of disease.  The lab's experimental expertise are highly multi-disciplinary, ranging from total protein chemical synthesis, X-ray crystallography, solution NMR, cell functional assays, and in vitro biophysics.

Education

B.S., Chemical Engineering, UCLA
Ph.D., Biophysics, UCSF

Awards & Professional Activities

Minority Access to Research Careers (MARC) U*Star Trainee      2012-14     UCLA

Howard Hughes Medical Institute (HHMI) Gilliam Fellow            2017-20      UCSF

Selected References

Mravic M, Thomaston JL, Tucker M, Solomon P, Liu L, DeGrado WF. Packing of Apolar Side Chains Enables Accurate Design of Highly Stable Membrane Proteins. Science. 2019, 363(6434), 1418-23

Litvinov RI*, Mravic M*, Zhu H, Weisel JW, DeGrado WF, Bennett JS. Unique Transmembrane Domain Interactions Differentially Modulate Integrin αvβ3 and αIIbβ3 Function. PNAS. 2019, 116(25),12295-12300

Dang B, Mravic M, Hu H, Schmidt N, Mensa B, DeGrado WF. SNAC-Tag for Sequence-specific Chemical Protein Cleavage. Nature Methods. 2019, 16, 319-22

*Mravic M, *Hu H, Lu Z, Bennett JS, Sanders CS, Orr AW, DeGrado WF. De Novo Designed Transmembrane Peptides Activating the α5β1 Integrin. Protein Engineering, Design, and Selection. 2018, 31(5), 181-190

*Dang B, *Wu H, *Mulligan V, Mravic M, Wu Y, Lemmin T, Ford A, Silva DA, Baker D, DeGrado WF. De Novo Design of Covalently Constrained Meso-size Protein Scaffolds with Unique Tertiary Structures. PNAS. 2017, 114(41), 10852- 10857

*Zhang SQ, *Kulp DW, *Schramm CA, Mravic M, Samish I, DeGrado WF. The Membrane-and Soluble-Protein Helix- Helix Interactome: Similar Geometry via Different Interactions. Structure. 2015, 23(3), 527-41