Fenghua Cai, Jianfeng He, Yunchuan Liu, Hongjiang Zhang
BCSLinker: automatic method for constructing a knowledge graph of venous thromboembolism based on joint learning
Frontiers in medicine
essay focuses debate warshel et al proponents preorganization menger nome proponents spatiotemporal effects source fast enzyme catalysis warshel model proposes main function enzymes push solvent coordinate toward transition state physicalorganic factors eg desolvation entropic effects ground state destabilization etc ostensibly contribute substantially rate indeed physical organic chemistry entirety claimed irrelevant enzymes active site preorganization applied warshel flagship enzyme ketosteroid isomerase discuss troubling issues ensuing analysis example concepts general acid general base known play role enzymes mechanism ignored text contrast spatiotemporal theory postulates enzymelike rates ie accelerations 108 occur two functionalities held rigidly contact distances less ca 3 numerous diverse organic systems shown bear experimentally many intramolecular systems distances functionalities known among fast intramolecular systems strain actually generated reaction thereby excluding steric compression source observed enzymelike rates finally account ends structural data four active sites enzymes obtained others showing contact distances substrate analogues enzyme knowledge contact distances less diameter water found universally among enzymes fact attribute extremely fast rates given assumption enzymes whatever particular mechanism obey elementary chemical principles