How fast fast-folding proteins fold in silico

- In NTP simulations CLN025 folded with τs of 0.279 μs at 293 K and 0.198 μs at 300 K.
- The experimental τs of CLN025 are 0.261 μs at 293 K and 0.137 μs at 300 K.
- In NTP simulations Trp-cage also folded with τs of 2.4 μs at 280 K and 0.8 μs at 300 K.
- The experimental τs of Trp-cage are 2.4 μs at 280 K and 1.4 μs at 300 K.
- These τs suggest that fast-folding proteins can fold in silico as fast as in experiments.

In reported microcanonical molecular dynamics simulations, fast-folding proteins CLN025 and Trp-cage autonomously folded to experimentally determined native conformations. However, the folding times of these proteins derived from the simulations were more than 4-10 times longer than their experimental values. This article reports autonomous folding of CLN025 and Trp-cage in isobaric-isothermal molecular dynamics simulations with agreements within factors of 0.69-1.75 between simulated and experimental folding times at different temperatures. These results show that CLN025 and Trp-cage can now autonomously fold in silico as fast as in experiments, and suggest that the accuracy of folding simulations for fast-folding proteins begins to overlap with the accuracy of folding experiments. This opens new prospects of developing computer algorithms that can predict both ensembles of conformations and their interconversion rates for a protein from its sequence for artificial intelligence on how and when a protein acts as a receiver, switch, and relay to facilitate various subcellular-to-tissue communications. Then the genetic information that encodes proteins can be better read in the context of intricate biological functions.