Just wondering if you ever observe theoretical energies less than the native, and if so what the science behind that is - or is that one of the things this project is trying to determine?

Just wondering if you ever observe theoretical energies less than the native, and if so what the science behind that is - or is that one of the things this project is trying to determine?

we do, and investigating why this happens is one of the main things I've been working on the past month or so. there are two possible causes: first, there actually could be some lower energy states of the protein, particularly in cases where the native structure we are using is in complex with other molecules, and second, the non native structures could have lower energy because of inaccuracies in our model. The second class is valuable because they point to ways in which we can improve the energy function and hence the predictions. The new app, to be released in a day or two, has a number of new test parameters based on these investigations.

in either case, finding lower energy than native structures is very important, and the large scale computing you all are doing provides an unprecedented way to find them

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