Abstract by Talmage Coates
Physics and Astronomy
Dennis Della Corte
Computational design of SAM enzymes
Radical S-adenesyl methionine (radical SAM) enzymes catalyze a wide range of reactions.
Redesigning such enzymes is a promising route for biocatalysis of compounds that may be challenging and/or hazardous to synthesize via traditional methods. Computational methods have been shown to drastically improve the efficiency of enzyme design in several cases.
As enzymes are dynamic by nature, accurately modeling the conformations taken by an enzyme can significantly contribute to the accuracy of computational predictions of the potential benefits of various mutations. In the present work, molecular dynamics (MD) has been utilized, in conjunction with statistical methods, to produce structures representative of the Boltzman ensemble. Starting from these structures, PyRosetta has been utilized to design mutations to optimize this reactivity. Upon completion of this in silico design, proposed mutations will be verified experimentally.
More effective multistate design could revolutionize many industries.