Abstract
We present a method to treat the solvent efficiently in hybrid quantum mechanical/molecular mechanical simulations of chemical reactions in enzymes. The method is an adaptation of an approach developed for molecular-mechanical free-energy simulations. The charges of each of the exposed ionizable groups are scaled, and the system is simulated in the presence of a limited number of explicit solvent molecules to obtain a reasonable set of structures. Continuum electrostatics methods are then used to correct the energies. Variations in the procedure are discussed with an emphasis on modifications from the original protocol. We illustrate the method by applying it to the study of a hydrolysis reaction in a highly charged system comprising a complex between the base excision repair enzyme uracil-DNA glycosylase and double-stranded DNA. The resulting adiabatic reaction profile is in good agreement with experiment, in contrast to that obtained without scaling the charges.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Theoretical Chemistry Accounts: Theory, Computation, and Modeling (Theoretica Chimica Acta)
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
