Table 3. Comparison of Different Parameters Used by Wan et al.⁵³ for the Original TIES Calculations of the BRD4 Inhibitor Transformations with Those Used in This Study for the TIES Calculations Using the pmemdGTI Software Package.

parameter	original TIES	pmemdGTI
MD engine	NAMD	AMBER
processor	CPU	GPU
method	dual topology	single topology
ensemble	NPT (300 K, 1 bar)	NVT (300 K)
timestep	2 fs	1 fs
electrostatic cutoff	12 Å	9 Å
electrostatic decoupling/coupling	0–0.55/0.45–1 (see ref (53))	0–1
softcore potential	vdW	vdW + elec
buffer size	14 Å	11 Å
number of λ-windows	13 (0, 0.05, 0.1, ···, 0.9, 0.95, 1)	11 (0,0.1, ···, 0.9,1)
initial structures for each λ	minimization	minimization, sequential equl. (1.4 ns/λ)
simulation run	2 ns equl., 4 ns prod.	1 ns equl., 4 ns prod.
number of replicas	5	10