unfortunately there is no automatic procedure to do this. Amber is a great
tool, but you need to tell it what simulation you want to do. For
calculating binding, you need to know something about the process (meaning
you need a hypothesis) that you can test with a simulation. the real
problem with what you propose is that when the one peptide binds to the
others, there could be many different kinds of conformational changes
involved, and they can be very slow. Umbrella sampling lets you use a
restraint so you don't have to sample along the restraint coordinate, but
if there are motions that are slow that are not described by the restraint,
umbrella sampling won't help. for example, if you use the distance between
the centers of mass of the peptides, you will get a PMF, but it will be
very hard to average over all of the internal conformational states of the
peptide at each distance.
I suggest that you find articles in good journals that successfully do the
kind of thing you're trying, and then to follow their methods. if you can't
find any work that has shown success, then consider it to be a difficult
research problem and you will probably have to put a lot of effort into
developing good methods, and including proper controls to show that they
work in cases where you can validate them. overall, I would think that
doing what you seem to want to do (calculate the free energy of adding 1
very flexible molecule to a cluster of other very flexible molecules) is
going to be very, very difficult without you being able to include more
information to reduce the amount of conformational sampling that would need
to be done.
On Mon, Dec 22, 2014 at 4:22 PM, Helen Lvy <helenyuan0302.outlook.com>
wrote:
>
>
>
>
> Dear all users,
>
> I'm new to umbrella sampling using Amber, hope someone could help me or
> giving me some suggestions.
>
> Now I'm struggling simulate one peptide joining into the aggregate of
> other five peptides, and I need to calculate their free energy changing in
> this process. According to the tutorial 17, I figure out that a disang file
> needs to be defined. However, I have no idea how to define the distance
> restrain for different peptides, not for each atoms.
>
> Someone is familiar with this? Great appreciate!
>
> Sincerely,
>
> Best regards,
>
> Helen
>
>
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>
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Received on Mon Dec 22 2014 - 16:00:02 PST
