The use of computational library screens in order to aid with the development of drugs and the analysis of compounds is now widespread. The main advantage of such methods is the possibility to automate processes where the experimental cost of testing may be too high to be prove profitable to use laboratory techniques. By employing a virtual screen, previously intractable volumes of data may be accessed at a smaller cost.Based on this observation, we are developing a computational tool for the mutagenesis of proteins. This protocol can be used to mutate residues in a protein or peptide and analyse the effects of that mutation on the protein's properties or interaction with another compound. This, in turn, can lead to the rational design of proteins and can be an additional tool for their analysis.The protocol was developed with the AMBER MD package, and special emphasis was given to its compatibility with other tools in the same suite. It is able to mutate at will between almost any pair of amino acids, in a highly automated process. Testing is ongoing to compare with current similar protocols and to determine the reliability of these computationally generated values in relation to experimental data, with encouraging results. In particular we have been testing the computational growth of chemical staples on peptides, which has had, so far, quite good agreement with previously published laboratory results.The ultimate aim of this protocol is to be employed in antibody design, though its flexible and versatile nature makes it possible to be used in any system that might require amino acid mutations.

Development of a new protocol for computational site-directed mutagenesis

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.