TrajMine — mechanism report

Mechanistic summary
The 250-ns alanine dipeptide simulation reveals four metastable macrostates with a highly asymmetric population distribution (63%, 34%, 3%, and 0.2%), connected by slow conformational transitions characterized by an MSM relaxation timescale of 1264 ps and a dominant tICA timescale of 281 ps. The slowest tICA collective variable, capturing backbone dihedral transitions with a ~280 ps decorrelation time, separates the two dominant basins that account for 97% of the ensemble. Mean first-passage times between the two most-populated states are highly asymmetric (714 ps vs 41,798 ps), indicating the minor state (34%) represents a kinetic trap requiring rare barrier-crossing events to escape to the global minimum. Contact map differences between these states likely reflect the classical C7eq ↔ αR transition in alanine dipeptide, where reorganization of the peptide backbone hydrogen bonding pattern drives the conformational exchange on the nanosecond timescale.

Kinetics — Markov State Model
Slowest MSM implied timescales: 1264 ps, 75 ps, 34 ps, 24 ps
tICA timescales: 281 ps, 73 ps, 8 ps
100 microstates → 4 PCCA+ macrostates   (lag 10 ps)
Mean first-passage times (ps):

	M0	M1	M2	M3
M0	0	714	1637	1396
M1	41798	0	1590	1350
M2	81045	39796	0	158
M3	80950	39702	304	0

Residue-level drivers
Most flexible: ALA2
Dominant-motion drivers (PC1): ALA2