Alex T. Grigas

Protein Biophysics · Soft Matter · Computational Biology

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Alex T. Grigas

About

I'm a computational biophysicist studying how proteins fold and how tissues flow. I received my Ph.D. in computational biology and bioinformatics from Yale University in 2024, advised by Corey O'Hern. My doctoral work was equal parts protein structural informatics and soft matter physics. Since 2024, I have been a postdoctoral researcher in the Syracuse Physics Department, working with M. Lisa Manning. In collaboration with Alessandro Mongera, we have developed new discrete element models for dynamic and sparse tissues under tension. See below for highlights of my work and my CV.

Research

contact map vs burial

Residue burial encodes a protein's fold

Protein folding prediction Information theory Decoy detection

How much information is needed to fold a protein? We find that surprisingly, a simple binary representation of whether each residue is either buried in the core or exposed on the surface is enough information to discriminate the correct protein fold from incorrect folds. Moreover, we find that residue burial was the most efficient encoding of a protein's fold, needing only 0.37 bits per residue; more efficient than contact maps, secondary structure, hydrogen bonding satisfaction and even machine learned embedding like Foldseek 3Di. Check out our preprint linked below.

bioRxiv GitHub
Protein jamming transition

Protein folding as a jamming transition

Protein Physics Jamming All-atom modeling

Protein cores all pack to the same density (φ ≈ 0.55), but there has been no physical explanation for why. We show this value marks the onset of a jamming transition: as hydrophobic interactions drive collapse, the core undergoes a floppy-to-rigid transition with the same power-law scaling hallmarks seen in jammed particulate systems. To demonstrate this, I built a new all-atom protein model from scratch — using only hard-core repulsion, bond geometry, and weak hydrophobic attraction — that achieves near-zero Ramachandran and side-chain dihedral outliers without explicit dihedral restraints, staying within ~1 Å RMSD of crystal structures at jamming onset and refolding from partially unfolded states. Check out our paper published in PRX Life linked below.

PRX Life GitHub
CIL-Crawling
CIL-Pulling

Sparse mesenchymal cell networks as a fluid under tension

Active Matter Tissue Mechanics Morphogenesis

Embryonic mesenchymal tissues are sparse, under tension, and flow like a fluid — a combination that naively should be unstable. We developed a new particle-based interaction model with hysteretic sticking and stochastic bond kinetics to show that contact inhibition of locomotion (CIL) resolves this paradox, generating a uniform, tensioned and fluid material. Check out our preprint linked below.

bioRxiv GitHub
Repulsive compression
Attractive collapse

Connecting polymer collapse and the onset of jamming

Jamming Polymer collapse Core packing

Protein cores pack to the same density as jammed repulsive amino acids — but proteins collapse via attraction, not compression. Is the correspondence deep or coincidental? I developed simulations of attractive and repulsive bead-spring polymers and disconnected disks to better understand the similarities between polymer collapse and compressed packings. See our work in Phys. Rev. E. linked below.

Phys. Rev. E

CV

Download Full CV

Positions & Education

Postdoctoral Researcher — Syracuse University 2024 – present
Physics Dept. · Adviser: M. Lisa Manning
Ph.D. in Computational Biology & Bioinformatics — Yale University 2018 – 2024
With distinction · Integrated Graduate Program in Physical & Engineering Biology · Adviser: Corey S. O'Hern
B.S. Biochemistry & Molecular Biology / B.A. Philosophy — Penn State 2014 – 2018
Magna cum laude / Summa cum laude · Honors Thesis with Christine Keating

Publications

  1. J. A. Logan, J. Sumner, A. T. Grigas, M. D. Shattuck, and C. S. O'Hern, "The effect of stereochemical constraints on the structural properties of folded proteins," Phys. Rev. E 112 (2025)
  2. A. T. Grigas, Z. Liu, J. A. Logan, M. D. Shattuck, and C. S. O'Hern, "Protein folding as a jamming transition," PRX Life 3 (2025)
  3. S. Viswanath, D. Bhaskar, D. R. Johnson, J. F. Rocha, E. Castro, J. D. Grady, A. T. Grigas, M. A. Perlmutter, C. S. O'Hern, and S. Krishnaswamy, "ProtSCAPE: Mapping the landscape of protein conformations in molecular dynamics," Molecular Machine Learning Conf. (2024)
  4. A. T. Grigas, A. Fisher, M. D. Shattuck, and C. S. O'Hern, "Connecting polymer collapse and the onset of jamming," Phys. Rev. E 109 (2024)
  5. Z. Liu, A. T. Grigas, J. Sumner, E. Knab, C. M. Davis, and C. S. O'Hern, "Identifying the minimal set of distance restraints for FRET-assisted protein structural modeling," Protein Science 33 (2024)
  6. A. T. Grigas, Z. Liu, L. Regan, and C. S. O'Hern, "Core packing of well-defined x-ray and NMR structures is the same," Protein Science 31 (2022)
  7. A. T. Grigas, Z. Mei, J. D. Treado, Z. A. Levine, L. Regan, and C. S. O'Hern, "Using physical features of protein core packing to distinguish real proteins from decoys," Protein Science 29 (2020)
  8. Z. Mei, J. D. Treado, A. T. Grigas, Z. A. Levine, L. Regan, and C. S. O'Hern, "Analyses of protein cores reveal fundamental differences between solution and crystal structures," Proteins: Struct. Func. Bioinf. 88 (2020)
  9. F. P. Cakmak, A. T. Grigas, and C. D. Keating, "Lipid vesicle-coated complex coacervates," Langmuir 35 (2019)
  10. K. Reiss, U. N. Morzan, A. T. Grigas, and V. S. Batista, "Water network dynamics next to the oxygen-evolving complex of photosystem II," Inorganics 7 (2019)

Under Review & In Preparation

  1. A. T. Grigas, R. S. Negi, E. Maniou, G. L. Galea, A. Michaut, A. Mongera, and M. L. Manning, "Sparse mesenchymal cell networks as a fluid under tension" — Under review, Nature Physics (2025)
  2. J. Sumner, N. Brandt, G. Meng, A. T. Grigas, A. Cordoba, M. D. Shattuck, and C. S. O'Hern, "Assessment of scoring functions for computational models of protein-protein interfaces" — Under review, Phys. Rev. E (2025)
  3. A. T. Grigas, J. Sumner and C. S. O'Hern, "Residue burial encodes a protein's fold" — Under review, Phys. Rev. Letters (2026)
  4. A. T. Grigas and M. Lisa Manning "A fluid under tension" — In preparation (2026)

Selected Talks

Contributed Talk — APS March Meeting 2022 – 2026
Invited Mini-Symposium Talk — Society for Mathematical Biology 2025
Invited Talk — Computational Protein Design Network 2022
Invited Talk — APS March Meeting 2021

Teaching & Mentorship

Research Mentorship
19 mentees across O'Hern and Manning groups: graduate students, postbacs, undergraduates, and high school interns
Teaching Assistant — Yale University
Biological Physics, Integrated Workshop, Intro to Computing, Dynamics · Avg. 4.4/5 student evaluations

Technical Skills

Languages Python C/C++
Scientific Computing NumPy SciPy PyTorch Matplotlib
Structural Biology ESM2 AlphaFold RosettaFold GROMACS BioPython VMD
Infrastructure HPC SLURM HTCondor Docker Git

Awards

1st Place, 5-Minute Thesis — USNC/TAM 2024
Finn Wold & Protein Science Young Investigator Travel Award 2023
Protein Society Graduate Student Poster Award 2023
Paul Axt Prize — Penn State Schreyer Honors College 2018