Re: Computational studies of H5N1 hemagglutinin binding with SA-α-2, 3-Gal and SA-α-2, 6-
Why compute?
The three-dimensional configurations of the Hemagglutinin molecule and the way that the binding site interacts with the a2,3 or a2, 6 sialic acid terminal in the glycocalyx gives an indication of the strength and therefore the likelihood of successful bonding. As it is impossible to see this interaction the best that we can do is to visualise it with the aid of a computer model, this has the added advantage that it allows us to envisage the interactions of hypothetical binding site arrangements. As I noted in an earlier post this will allow us to calculate in advance whether changes to the existing binding site structure will increase would decrease the likelihood of affective binding to an alpha 2, 6 sugar. If we begin to see mutations in the known binding site domains which should be able to predict whether these a likely to give stronger alpha 2, 6 binding and therefore increase the chance of human infection. Computer modeling is the only way that we going to be able to do this.
The long thread in Mingus's lab covered such a lot of ground I think it's almost impossible for me condense this.
A few of the points which are worth taking from that long thread are
LP flu has a short cleavage site and is fussy about which proteases can cleave it, HP flu like 1918 and H5N1 can be cleave to buy a wide range of ubiquitous proteases.
The interactions between the different RNA strands is not simple, virulence is difficult to pin down to a sequence on any given strand, mutations in one area on a given strand can turn on, or off, virulence and yet the same mutation at the same point in another virus does not have the same effect. Another example of the interaction between the different proteins coded for by the RNA segments is the ability of neuraminidase to sequester proteases capable of cleaving Hemagglutinin.
Another point of discussion was the effect of passaging the virus in either chicken or MDCK (mouse) cells as the choice of cell will affect the evolution of the virus.
The discussion in the thread then began to look at the role of the proteases in cleavage, as mentioned earlier in seasonal flu Clara protease is normally responsible for cleaving the HA 0 into its two active parts HA1 & HA2 but there are some gram negative bacteria which can produce suitable proteases in the LRT and allow infection via this route.
I hope this helps, I am trying out a new bit of voice recognition software so if there are some odd words or spellings in here that is why.
Why compute?
The three-dimensional configurations of the Hemagglutinin molecule and the way that the binding site interacts with the a2,3 or a2, 6 sialic acid terminal in the glycocalyx gives an indication of the strength and therefore the likelihood of successful bonding. As it is impossible to see this interaction the best that we can do is to visualise it with the aid of a computer model, this has the added advantage that it allows us to envisage the interactions of hypothetical binding site arrangements. As I noted in an earlier post this will allow us to calculate in advance whether changes to the existing binding site structure will increase would decrease the likelihood of affective binding to an alpha 2, 6 sugar. If we begin to see mutations in the known binding site domains which should be able to predict whether these a likely to give stronger alpha 2, 6 binding and therefore increase the chance of human infection. Computer modeling is the only way that we going to be able to do this.
The long thread in Mingus's lab covered such a lot of ground I think it's almost impossible for me condense this.
A few of the points which are worth taking from that long thread are
LP flu has a short cleavage site and is fussy about which proteases can cleave it, HP flu like 1918 and H5N1 can be cleave to buy a wide range of ubiquitous proteases.
The interactions between the different RNA strands is not simple, virulence is difficult to pin down to a sequence on any given strand, mutations in one area on a given strand can turn on, or off, virulence and yet the same mutation at the same point in another virus does not have the same effect. Another example of the interaction between the different proteins coded for by the RNA segments is the ability of neuraminidase to sequester proteases capable of cleaving Hemagglutinin.
Another point of discussion was the effect of passaging the virus in either chicken or MDCK (mouse) cells as the choice of cell will affect the evolution of the virus.
The discussion in the thread then began to look at the role of the proteases in cleavage, as mentioned earlier in seasonal flu Clara protease is normally responsible for cleaving the HA 0 into its two active parts HA1 & HA2 but there are some gram negative bacteria which can produce suitable proteases in the LRT and allow infection via this route.
I hope this helps, I am trying out a new bit of voice recognition software so if there are some odd words or spellings in here that is why.
