Data from: Molecular exaptation by the integrin αI domain

Hollis, Jeremy1 ; Chan, Matthew C.1 ; Campbell, Melody1

Published Aug 13, 2025 on Dryad. https://doi.org/10.5061/dryad.wstqjq2zv

Data files

Aug 13, 2025 version files 103.11 GB

aEb7_LFA1.zip

25.89 GB
i-domains.zip

77.22 GB
README.md

7.95 KB

Abstract

Integrins bind ligands between their alpha (α) and beta (β) subunits and transmit signals through conformational changes. Early in chordate evolution, some α subunits acquired an "inserted" (I) domain that expanded integrin’s ligand-binding repertoire but obstructed the ancestral ligand pocket, seemingly blocking conventional integrin activation. To understand the ancestral conformational dynamics of the integrin I domain, we performed all-atom molecular dynamics simulations on a representative sample of integrin I domains, sister clade collagen-derived vWFA domains, and the ancestral reconstruction AncI. We further investigated the effect of amino acid substitution on the internal ligand of αLβ2 bound with ICAM-1 and αEβ7 bound to E-cadherin. All simulations were performed using OpenMM 7.7.0 (I-domain systems) or OpenMM 8.2.0 (integrin headpiece systems) employing AMBER19ffSB force field, OPC water model, and 12-6-4 Li Merz ion parameters. Simulations were performed on either the Fred Hutch Cancer Center clusters on Nvidia GTX 2080 or in-house workstations on Nvidia GTX 3090. Trajectory snapshots were saved every 100 ps during production simulations.

Provided Files

The dataset contains molecular dynamics trajectories analyzed for the manuscript titled "Molecular exaptation by the integrin αI domain", Science Advances, 2015. Two sets of simulations were performed: 1) simulations of various integrin I-domains initially bound to different divalent cations (i-domains/), and 2) simulations of the αEβ7 and LFA1 headpiece simulations (aEb7-LFA1/).

i-domains.zip/ files for I-domain simulations. Includes:
- strip-traj/ - trajectories in .xtc file format
- ref/ - reference trajectories for RMS analysis
- prmtop/ - topology file in .prmtop file format
aEb7_LFA1.zip/ files for αEβ7 and LFA1 simulations. Includes:
- wrap-traj/ - trajectories in .xtc file format
- ref/ - reference trajectories for RMS analysis
- prmtop/ - topology file in .prmtop file format

Simulation details

All simulations were performed using OpenMM 7.7.0 (I-domain systems) (Ref. 1) or OpenMM 8.2.0 (Ref 2.) (integrin headpiece systems) employing AMBER19ffSB force field (Ref. 3), OPC water model, and 12-6-4 Li Merz ion parameters (Ref. 4). The proteins were solvated in a periodic truncated octahedron with OPC water molecules and 150mM NaCl. Langevin dynamics was performed using a Langevin integrator with an integration timestep of 4 fs and collision rate of √2 ps-1 and hydrogen mass repartitioning (Ref. 5). Pressure was maintained using a Monte Carlo barostat with an update frequency of 100 steps. Nonbonded interactions were calculated with a distance cutoff of 10Å. Trajectory snapshots were saved every 100 ps during production simulations. Trajectory lengths and number of replicates of each simulated system are listed in the Table below.

Integrin headpiece

System	Ligand	Initial Model	Replicates	Trajectory Length (per replicate, μs)
αEβ7	E-cadherin	This study	4	1.0
αEβ7_E372D	E-cadherin	This study	4	1.0
αEβ7_E372A	E-cadherin	This study	4	1.0

LFA1

System	Ligand	Initial Model	Replicates	Trajectory Length (per replicate, μs)
LFA1	ICAM-1	Homology model	6	1.0
LFA1_IDGT	ICAM-1	Homology model	6	1.0
LFA1_VDGT	ICAM-1	Homology model	6	1.0
LFA1_IAGT	ICAM-1	Homology model	6	1.0
LFA1_SNTD	ICAM-1	Homology model	6	1.0
LFA1_GRPQ	ICAM-1	Homology model	6	1.0

I domain

System	Ligand	Initial Model	Replicates	Trajectory Length (per replicate, μs)
αE	Mg²⁺	This study	10	2.4
αE	Mn²⁺	This study	10	2.4
αE	Ca²⁺	This study	10	2.4
αL	Mg²⁺	PDB: 3F74	10	2.4
αL	Mn²⁺	PDB: 3F74	10	2.4
αL	Ca²⁺	PDB: 3F74	10	2.4
α2	Mg²⁺	PDB: 5HJ2	10	2.4
α2	Mn²⁺	PDB: 5HJ2	10	2.4
α2	Ca²⁺	PDB: 5HJ2	10	2.4
XP_032834731	Mg²⁺	Alphafold2	10	2.4
XP_032834731	Mn²⁺	Alphafold2	10	2.4
XP_032834731	Ca²⁺	Alphafold2	10	2.4
co6a6	Mg²⁺	Alphafold3	10	2.4
co6a6	Mn²⁺	Alphafold3	10	2.4
co6a6	Ca²⁺	Alphafold3	10	2.4
co6a5	Mg²⁺	Alphafold3	10	2.4
co6a5	Mn²⁺	Alphafold3	10	2.4
co6a5	Ca²⁺	Alphafold3	10	2.4
vwa129	Mg²⁺	Alphafold3	10	2.4
vwa129	Mn²⁺	Alphafold3	10	2.4
vwa129	Ca²⁺	Alphafold3	10	2.4
coea1	Mg²⁺	Alphafold3	10	2.4
coea1	Mn²⁺	Alphafold3	10	2.4
coea1	Ca²⁺	Alphafold3	10	2.4
AncI	Mg²⁺	Alphafold3	10	2.4
AncI	Mn²⁺	Alphafold3	10	2.4
AncI	Ca²⁺	Alphafold3	10	2.4
RPN10	None	PDB: 5LN1	10	2.4

References:

P. Eastman, J. Swails, J. D. Chodera, R. T. McGibbon, Y. Zhao, K. A. Beauchamp, L.-P. Wang, A. C. Simmonett, M. P. Harrigan, C. D. Stern, R. P. Wiewiora, B. R. Brooks, V. S. Pande, OpenMM 7: Rapid development of high performance algorithms for molecular dynamics. PLoS Comput. Biol. 13, e1005659 (2017).
P. Eastman, R. Galvelis, R. P. Peláez, C. R. A. Abreu, S. E. Farr, E. Gallicchio, A. Gorenko, M. M. Henry, F. Hu, J. Huang, A. Krämer, J. Michel, J. A. Mitchell, V. S. Pande, J. P. Rodrigues, J. Rodriguez-Guerra, A. C. Simmonett, S. Singh, J. Swails, P. Turner, Y. Wang, I. Zhang, J. D. Chodera, G. De Fabritiis, T. E. Markland, OpenMM 8: Molecular dynamics simulation with machine learning potentials. J. Phys. Chem. B 128, 109–116 (2024).
C. Tian, K. Kasavajhala, K. A. A. Belfon, L. Raguette, H. Huang, A. N. Migues, J. Bickel, Y. Wang, J. Pincay, Q. Wu, C. Simmerling, ff19SB: Amino-Acid-Specific Protein Backbone Parameters Trained against Quantum Mechanics Energy Surfaces in Solution. J. Chem. Theory Comput. 16, 528–552 (2020).
A. Sengupta, Z. Li, L. F. Song, P. Li, K. M. Merz Jr, Parameterization of Monovalent Ions for the OPC3, OPC, TIP3P-FB, and TIP4P-FB Water Models. J. Chem. Inf. Model. 61, 869–880 (2021).
C. W. Hopkins, S. Le Grand, R. C. Walker, A. E. Roitberg, Long-Time-Step Molecular Dynamics through Hydrogen Mass Repartitioning. J. Chem. Theory Comput. 11, 1864–1874 (2015).

Dataset usage

Trajectories (.xtc) may be visualized using VMD by loading the corresponding topology file (.prmtop). Alternatively, trajectories and topologies may be loaded in open-sourced analysis packages such as MDTraj, MDAnalysis, and pytraj.