it is very helpful, thank you every much!
On 8/9/05, Yong Duan <duan.ucdavis.edu> wrote:
>
> Dear Haixiao:
>
> I noticed your questions on AMBER mail reflector.
>
> First, B-factors are composite measures of disorder and dynamics, disorder
> in crystalline environment and dynamics of molecular motion at the time when
> X-ray data is taken. From an ensemble average perspective, the two are
> closely related. Since X-ray data reflects an ensemble average, both
> disorder and dynamics will show up as disorder. In a sense, B-factors
> provide an ensemble averaged measure of dynamics and disorder. From this
> perspective, indeed, experimental B-factors should always be larger than
> calculated ones since a) simulation time is always, for the time being,
> shorter than the experimental time scales by orders of magnitude and b) we
> may never have as many molecules in the system as what is available in any
> crystal and c) global translation and rotation are removed before B-factor
> calculation. However, this is an overly simplified interpretation.
>
> Second, B-factors are simplified measures of rather complex processes. Now,
> you've done some simulation and perhaps realized already that large-scale
> motion is typically anharmonic. Depending on your simulation time,
> large-scale dynamics, which contributes to your large calculated B-factors,
> most likely involved some degree of conformational change. The movement is
> typically anharmonic. Yet, you calculated B-factors using a harmonic
> assumption. This is part of the simplification.
>
> Third, the experimental B-factors were measured in crystalline environment
> and your simulations are most likely done in solution. The difference is
> quite substantial. In the crystalline environment molecules are in close
> contacts. In many cases (probably safe to say in most cases), the dynamic
> parts (e.g. loops) which contributes to the large calculated B-factors
> typically form crystal contacts with neighboring molecules. As a consequence
> of the crystal contacts, their measured B-factors are much smaller because
> they can no longer move much. In many cases, this is the most important
> contributor to the difference between calculated and experimental B-factors.
>
> Fourth, there are also cases where very-high resolution of crystals were
> obtained. Because of the high resolution, the measured B-factors are
> typically small. In these cases, B-factors calculated from simulation can be
> notably higher than the experimental ones throughout the molecule (not
> limited to the dynamic parts). This is again largely due to the environment.
> The high-resolution crystals are typically very well packed. On the other
> hand, your simulations are done in solution and the molecule is entirely
> solvated in solution, alone. Serious comparison should be done in the
> crystalline environment.
>
> Fifth, we should always keep in mind the approximation associated with our
> simulation parameters besides the limited time and number of molecules. This
> inevitably contributes to the error and discrepency. However, at this level,
> I seriously doubt that B-factors are sensitive enough to be good measures
> for comparison. When simulations are done in the same crystaline environment
> with the right amount of salt, water, ions, etc., agreement has been
> exceptionally good. Of course, this does not mean that our simulations are
> perfect. It just means that the measure is not sensitive enough to pick up
> the difference.
>
> In summary, differences between calculated and experimental B-factors are
> expected largely because of the substantial differences between the
> environments.
>
> yong
>
>
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Received on Tue Aug 09 2005 - 07:53:00 PDT
