Corozzi, Alessandro

Dette ph.d. projekt omhandler udviklingen af en ny beregningsmetode der har potentiale for at udvide vores forståelser af enzymatisk katalyse med atomar detaljegrad. Nuværende teoretiske metoder der beskriver kemiske reaktioner er primært baseret på kvantemekanik (QM): elektronstrukturberegninger der benytter approksimationer til QM teori til at beskrive molekylær struktur. At modelere enzymatiske rekationer er udenfor rækkevidde ved brug af disse metoder da størrelsen af det betragtede system resulterer i mange-partikel ligninger der er for svære at løse selv for simple metoder såsom Hartree-Fock (HF). Et andet alternativ er klassiske modeller normalt omtalt som molekyl-mekanik (MM) der bruger Newtons ligninger til at beskrive molekylære systemer. Med disse metoder er det muligt at beskrive et helt enzym med relativt få beregningsmæssige ressourcer men til gengæld er der ingen mulighed for at beskrive kemiske reaktioner. Kort sagt, på den ene side haves QM metoder der kan beskrive kemiske reaktioner men er begrænset i størrelsen af det kemiske system er kan behandles, mens der på den anden side have MM metoder der kan beskrive meget store systemer uden kemiske reaktioner. Det reaktive kraftfelt (ReaxFF) er en simplificeret model der forsøger at danne bro mellem kvantekemiske metoder og de klassiske molekyl-mekaniskemetoder med det formål at muliggøre studier af kemiske reaktioner der finder sted undervejs i en simulering. Med udgangspunkt i et publiceret ReaxFF kraftfelt udviklet til beskrivelse af aminosyren glysin er der udviklet, optimeret og anvendt et nyt ReaxFF kraftfelt, ProtReaxFF, til beskrivelse af enzymkatalyse.This PhD project eassay is about the development of a new method to improve our understanding of enzyme catalysis with atomistic details. Currently the theory able to describe chemical systems and their reactivity is quantum mechanics (QM): electronic structure methods that use approximations of QM theory to describe molecular structure. Modeling enzyme reactions is anyway still inacessible to these methods because the size of the problem would result in many-particle equations too complicated to be solved even with rather crude approximations such as HartreeFock (HF). At the same time there are ordinary classical models - the molecular mechanics (MM) force-fields - that use newtonian mechanics to describe molecular systems. At this level it is possible to include the entire enzyme system still having light equations but renouncing to an easy modeling of chemical transformation during the simulation time. In short: on one hand we have accurate QM methods able to describe reactivity but limited in the size of the system to describe, while on the other hand we have molecular mechanics and ordinary force-fields that are virtually unlimited in size but unable to straightforwardly describe chemical reactivity. A reactive force-field (ReaxFF) is a simplified model that aims to bridge the gap between quantum chemistry methods to the ordinary force-fields of the classical molecular mechanics methods, enabling MM to model chemical reactions as a QM method with bond forming and breaking events during the simulation time. This has been accomplished by simply introducing anharmonicities in the potential energy terms of the force-field. Starting from a published ReaxFF force-field developed for modeling glycine aminoacid a novel ReaxFF force-field, ProtReaxFF, has been developed, optimized and applied to enzyme catalysis reactions

Online Research Database In Technology

Computational Enzymology, a ReaxFF approach

http://orbit.dtu.dk/ws/files/74276462/Corozzi_PhD_Thesis_LR..PDF

Computational Enzymology, a ReaxFF approach

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Online Research Database In Technology