l - People

Conclusions
At the beginning of this work we laid out an overall strategy for studying the flexibility
and motion of hinge bending proteins. Our first step was to relate hinges to sequence
features, gaining key insights into the physicochemical and structural nature of hinges,
and their role in catalysis. These were confirmed and expanded upon in structural studies
of hinges, yielding several accurate methods for hinge prediction. The methods were
integrated into the HingeMaster web tool which is being used regularly by the scientific
community. I have had many discussions and several collaborations with people using
the server; these have been educational for me and I hope useful for them.
Identification of the hinge opened the door to prediction of motion involving the hinge.
The Conformation Explorer followed from this work and was used to solve two
outstanding problems in the prediction of large scale conformational change: how to
generate alternate conformations economically and reliably, and how to choose the
desired conformer from an ensemble.
Our work here is not finished, though. To be truly useful the Conformation Explorer
needs to be accessible to experimentalists with no time or inclination to install and use
what is necessarily a complex piece of code. We are far along the road to making a new
web server that does this; in fact we used it to do all of the computations and make most
of the images in Chapter 5. More work remains, which hopefully won’t take long.
The HingeMaster and Conformation Explorer themselves are preceded by the morph
server, which remains popular with users. Werner Krebs built much of the original
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