MD Contact-Dynamics Analyzer

What it is

End-to-end residue-resolved CONTACT-DYNAMICS for intrinsically disordered proteins and biomolecular condensates, mirroring the cascade-computing pipeline (Gaurav et al., MUT-16 FFR, eLife 2025). Three modes: SIMULATE runs a coarse-grained MD engine to GENERATE the trajectory, detects contacts, and reduces the kinetics - the full pipeline in one plugin. Two force fields: HPS (sequence-specific: Ashbaugh-Hatch hydrophobicity + Debye-Huckel electrostatics, one bead/residue, REAL units so lifetimes come out in ns, with HVP-style cell lists for O(N) neighbour search) and a generic bead-spring model (reduced units). SYNTHETIC produces a record with a KNOWN mean lifetime so the method is seen recovering ground truth; RECORD consumes a pasted all-atom contact record. From the record it derives, exactly: the dual-cutoff contact-LIFETIME distribution (median and mean, transient single-frame excursions bridged within a weak cutoff, breaks_tol=1), contact FREQUENCY / occupancy (raw and abundance-normalized), resolved per residue-ID pair and per residue-type pair. The reductions run through the real GeoNum kernel for a canonical drift-shade trust verdict; the O(N) cell lists are validated to reproduce the brute-force forces exactly (matched-frame gate). Honest scope: coarse-grained (one bead/residue) dynamics are faster than all-atom, so absolute lifetimes are not directly comparable to all-atom ns; lambda is Kyte-Doolittle-normalized, sigma uniform 6 A; a WebGPU non-bonded kernel accelerates large systems, gated by a runtime self-check against the CPU reference with automatic fallback; feed RECORD mode an all-atom contact record for definitive biological numbers. Deterministic, in-browser, no AI / network / key.

Honest scope

Authorities cited

• Gaurav, K.; Bhardwaj, L.; et al. "Atomistic simulations reveal sub-microsecond contact dynamics in MUT-16 condensates." eLife (Reviewed Preprint) 2025, elifesciences.org/reviewed-preprints/111559. The MUT-16 FFR condensate contact-dynamics study whose downstream-metrics stage this mirrors (median contact lifetime ~9.8 ns; right-skewed distributions; dual-cutoff persistence).
• cascade_computing (comp-mol-biol), branch MUT16_FFR_v0.1: the parallelized HPC contact-analysis pipeline (Signac / Dask / pandas / HDF5) and the cont_params used here - delta_ha (strict cutoff) = 6 A, buffer = 0.4*sqrt(3) (weak cutoff extension), breaks_tol = 1, d_step = 1. github.com/comp-mol-biol/cascade_computing.
• Venkatakrishnan, A.J.; et al. getContacts geometric interaction criteria (salt bridge, cation-pi, pi-pi, hydrogen bond) - the upstream contact-detection logic the pipeline adopts (VMD-free). getcontacts.github.io.
• Gowers, R.J.; et al. "MDAnalysis: A Python Package for the Rapid Analysis of Molecular Dynamics Simulations." Proc. 15th Python in Science Conf. 2016, 98-105. Trajectory / hydrogen-bond analysis used upstream in the reference pipeline.
• Ashbaugh, H.S.; Hatch, H.W. "Natively Unfolded Protein Stability as a Coil-to-Globule Transition in Charge/Hydropathy Space." J. Am. Chem. Soc. 2008, 130(29), 9536-9542. The Ashbaugh-Hatch hydrophobicity-scaled Lennard-Jones potential used in the SIMULATE/HPS non-bonded force.
• Dignon, G.L.; Zheng, W.; Kim, Y.C.; Best, R.B.; Mittal, J. "Sequence determinants of protein phase behavior from a coarse-grained model." PLoS Comput. Biol. 2018, 14(1), e1005941. The HPS one-bead-per-residue coarse-grained model for IDP phase separation (Ashbaugh-Hatch + Debye-Huckel) that SIMULATE/HPS implements.
• Kyte, J.; Doolittle, R.F. "A simple method for displaying the hydropathic character of a protein." J. Mol. Biol. 1982, 157(1), 105-132. The hydropathy scale normalized to the HPS lambda used here (a defensible scale choice; HPS is scale-agnostic).
• Leimkuhler, B.; Matthews, C. "Rational construction of stochastic numerical methods for molecular sampling." Appl. Math. Res. Express 2013, 2013(1), 34-56. The BAOAB Langevin integrator used for constant-temperature (NVT) sampling in both MD engines.