BEGIN:VCALENDAR VERSION:2.0 PRODID:-//132.216.98.100//NONSGML kigkonsult.se iCalcreator 2.20.4// BEGIN:VEVENT UID:20250820T183334EDT-0181xsVD09@132.216.98.100 DTSTAMP:20250820T223334Z DESCRIPTION:Abstract:\n\nEnzymes were optimized by evolution to reach a max imum overall efficiency. However\, the available structural\, spectroscopi cal\, and biochemical information does not allow one to determine what the most important catalytic contributions are. Apparently\, in many cases it is crucial to use computer simulation approaches in order to find out the actual contribution from the different proposed catalytic factors (1-4). The talk will start with a clear definition of catalysis\, emphasizing the crucial need for a reference state. After a brief description of reliable approaches for the simulation of enzymatic reactions\, we will point out that all consistent simulation studies have concluded that enzymes work by using their preorganized polar environment to stabilize the transition st ate of the reacting substrates. This will be demonstrated by analyzing the effects of mutations in DHFR (5\,6)\, which has been used as evidence for the importance of dynamical effects. Additional support will be provided by analyzing the preorganization effect in KSI (7\,8). The second part of the talk will focus on the critical examination of non-electrostatic propo sals\, with particular attention being paid to the popular dynamical propo sal. It will be pointed out that a wide range of simulation techniques hav e been used to examine the magnitude of dynamical effects and their functi onal role (9\,10)\, and that it was found that these effects do not contri bute to catalysis (due to their similarity in both enzymes and solution) r egardless of the definition used. The discussion will then move to recent analyses of the relationship between flexibility and catalysis and correla ted motions and catalysis\, as well as between tunneling and catalysis. In all cases\, it will be demonstrated that we do not observe any catalytic effects (10). We will then consider studies of landscape effects that demo nstrate that the corresponding surfaces can be used to explore the dynamic s of the conformational and chemical motions in enzyme catalysis. (10\,11) . We will point out that preliminary studies along this line have conclude d that conformational changes can affect catalysis by changing the active site preorganization\, but that this is not associated with time dependent effects. It will be emphasized that enzymes work by using their preorgani zed polar environment to stabilize the transition state of the reacting su bstrates. This means that enzyme catalysis is due to enzyme-enzyme interac tions and not to enzyme-substrate interactions. Our recent advances in com puter aided enzyme design (12\,13) are discussed and analyzed.\n\n \n\nBio : \n\nArieh Warshel is a Distinguished Professor of Chemistry and Biochemi stry at the University of Southern California\, where he holds the Dana an d David Dornsife Chair in Chemistry. Prof. Warshel pioneered the field of computational enzymology\, being the driving force behind the development of computer simulations of the functions of biological systems that have a llowed scientists to understand how life processes operate on the protein level. Marrying classical and quantum mechanics\, he and colleagues Martin Karplus and Michael Levitt received the 2013 Nobel Prize for developing p owerful computer models that researchers use to understand complex chemica l interactions and create new drugs.\n DTSTART:20220906T170000Z DTEND:20220906T183000Z LOCATION:Room 10\, Maass Chemistry Building\, CA\, QC\, Montreal\, H3A 0B8\ , 801 rue Sherbrooke Ouest SUMMARY:Chemical Society Seminar: Arieh Warshel-How Do Enzymes Work and How Do They Not Work: Advances in Simulations and Computer Aided Enzyme Desi gn URL:/chemistry/channels/event/chemical-society-seminar -arieh-warshel-how-do-enzymes-work-and-how-do-they-not-work-advances-34006 9 END:VEVENT END:VCALENDAR