Table 3.

Elongation and error rates at [NTP] = 5 mM from kinetic network simulations.

Mism. catalyt. rate [s−1]	TL closing1 [ms−1]	AG (TL mism.)2 [kcal/mol]	E➔A rate [μs−1]	E/G/H/T/F rate scaling	Elongation rate [nt/s]	Error rate [1/1000]	Mismatch elongation rate3 [nt/s]
35	0.15	1	13.1	1	27.2 (0.07)	0.484 (0.068)	0.691 (0.014)
17.5	0.15	1	13.1	1	27.2 (0.05)	0.291 (0.067)	0.341 (0.010)
3.5	0.15	1	13.1	1	26.9 (0.10)	0.058 (0.021)	0.078 (0.003)
0.7	0.15	1	13.1	1	27.1 (0.04)	0.023 (0.013)	0.017 (0.001)
0.35	0.15	1	13.1	1	27.1 (0.06)	0.030 (0.015)	0.025 (0.014)
0.7	0.08	1	13.1	1	22.5 (0.04)	0.049 (0.030)	0.023 (0.005)
0.7	0.08/0.008	1	13.1	1	22.6 (0.06)	0.010 (0.010)	0.021 (0.002)
0.7	0.15/0.015	1	13.1	1	27.1 (0.08)	0.035 (0.019)	0.030 (0.007)
0.7	0.30	1	13.1	1	30.0 (0.09)	0.000 (0.000)	0.018 (0.005)
0.7	0.30/0.030	1	13.1	1	29.9 (0.08)	0.007 (0.007)	0.022 (0.005)
0.7	0.15	1	1.31	1	27.0 (0.06)	0.011 (0.008)	0.017 (0.003)
0.7	0.15	1	0.13	1	27.1 (0.08)	0.017 (0.009)	0.020 (0.001)
0.7	0.15	1	13.1	0.1	26.9 (0.04)	0.012 (0.006)	0.029 (0.009)
0.7	0.15	1	13.1	0.01	25.0 (0.06)	0.055 (0.015)	0.019 (0.002)
0.7	0.15	2	13.1	1	27.1 (0.06)	0.000 (0.000)	0.033 (0.031)
0.7	0.15	0	13.1	1	27.0 (0.06)	0.037 (0.014)	0.076 (0.007)
0.7	0.15/0.015	0	13.1	1	27.1 (0.17)	0.062 (0.033)	0.065 (0.005)
0.7	0.15	−2	13.1	1	25.6 (0.08)	1.622 (0.091)	0.568 (0.017)
0.7	0.15/0.015	−2	13.1	1	26.4 (0.09)	0.733 (0.067)	0.200 (0.000)
0.7	0.15	1	13.14	1	14.7 (0.03)	3.543 (0.316)	0.117 (0.004)
0.7	0.15	1	A5: kon=1 μs−1M−1		19.3 (0.02)	0.011 (0.011)	0.001 (0.000)
0.7	0.15	1	13.1	E6: kon=1 μs−1M−1	23.9 (0.05)	0.009 (0.006)	0.002 (0.000)
0.7	0.15	1	13.1	G7: kon=1 μs−1M−1	25.3 (0.03)	0.017 (0.008)	0.009 (0.004)

¹:two values indicate different TL closing rates for cognate/mismatch bases;

²:difference in free energy between open and closed trigger loop in the presence of a mismatched NTP in the active site (positive values indicate that TL closing is unfavorable in the presence of a mismatched NTP);

³: in the absence of cognate bases;

⁴: A-E rates were the same for mismatches and cognate bases;

⁵: NTPs enter A site directly (k_off=0 and exit via secondary pore is possible);

⁶: NTPs enter and exit E site directly bypassing G/H/T/F states (k_off=0.55 μs⁻¹, same as F-bulk rates);

⁷: NTPs enter and exit G site directly bypassing H/T/F states (k_off=0.55 μs⁻¹, same as F-bulk rates). Parameters that, consistent with experiment, result in overall elongation rates around 26–27 nt/s [40] and mismatch elongation rates that are reduced by about three orders of magnitude [44, 45] are shown in bold. Statistical errors estimated from block averaging by comparing results for 1,000 s segments from the kinetic simulations are given in parentheses.