RE: RE:Protein force fields
As it happens I have just reviewed the Rao and Teeter paper for our journal
club. I chose the paper for 3 reasons: a) It was being presented to
biochemists, b) I am a computational chemist, c) I liked the practicality
of the approach.
Martha Teeter is a crystalographer who has a long standing interest in proteins
related to a-purothionin (eg crambin which she also solved), but has limited
access to computing facilities (Microvax II). She clearly wants to find a
method that gives a good guess for solving protein structures by x-ray
methods. The paper presents a VERY rudimentary MD simulation using the
AMBER UA force field, in vacuo, with much of the structure constrained. This
is a very simple and unsophysticated approach, and in some ways it is perhaps
pleasantly surprising that it worked. However, there are a few notable
1) This is a purely anecdotal report.
2) Alpha-PT is highly homologous to Crambin and so a very good guess for the
MM/MD calculations was already available.
3) The MD was performed on a very small subset of the atoms (6 out of 46
4) Because of the particular nature of this protein (and its homologs) the
ends of the critical loop-region could be assumed to be in the correct
conformation, therefore extensive conformational restraints could be
5) The authors report that an unconstrained MD simulation (epsilon=1,in vacuo)
resulted in [hydrogen] bond breaking, but apparently did not test the
stability with (epsilon=4) which they went on to use for the partial
6) Although the authors refer to a 2ps equilibration period, there PE
data clearly shows equilibration was not reached until about 30 ps. This
is unimportant in context of their analysis, but without continuing the
trajectory for a longer period it is not possible to say how stable their
loop conformation really is.
The results are however interesting, particularly the sequential nature of
the changes in the backbone conformation. I think that if the system can be
modelled based on similar high homology the UA approach looks very interesting,
but it is very system dependant. It worked in this case but I think solvation
would have to be considered for more general studies.
Hope this sparks other comments and answers some of your questions,
Robert J. Woods, Ph.D.
Department of Biochemistry
University of Oxford
South Parks Road
Oxford, OX1 3QU