國(guó)際量子分子科學(xué)院院士高加力教授做客第301期化苑講壇
報(bào)告題目：Functional protein dynamics on enzyme catalysis
報(bào) 告 人 ：高加力教授
報(bào)告時(shí)間：2017年11月13日（周一）上午9:00
報(bào)告地點(diǎn)：化學(xué)樓二樓一號(hào)會(huì)議室
報(bào)告人簡(jiǎn)介：
高加力，教授，國(guó)際量子分子科學(xué)院院士，國(guó)家計(jì)劃。1982年在北京大學(xué)獲得學(xué)士學(xué)位，1987年在美國(guó)普渡大學(xué)獲得博士學(xué)位，同年前往美國(guó)哈佛大學(xué)從事博士后研究。1990-1994年擔(dān)任美國(guó)紐約州立大學(xué)助理教授，1994-1997年擔(dān)任美國(guó)紐約州立大學(xué)副教授，1997-1999年擔(dān)任美國(guó)州立大學(xué)教授，2000年-至今，擔(dān)任美國(guó)明尼蘇達(dá)大學(xué)教授。高加力教授一直致力于生物大分子體系的研究。主要包括蛋白動(dòng)力學(xué)，酶催化，生物體系反應(yīng)及分子自組裝，生物物理和計(jì)算方法的發(fā)展。目前主要致力于以下幾個(gè)方面的研究：1）生物大分子體系全量子化學(xué)方法；2）多態(tài)密度泛函理論；3）生物分子的相互作用與酶催化；4）溶劑效應(yīng)、反應(yīng)活性與物質(zhì)結(jié)構(gòu)的研究。
高加力教授曾獲世界理論導(dǎo)向化學(xué)家協(xié)會(huì)（WATOC）頒發(fā)的狄拉克獎(jiǎng)?wù)隆鼗舴蚵菽昙o(jì)念獎(jiǎng)、IBM學(xué)院獎(jiǎng)學(xué)金等國(guó)際大獎(jiǎng)。獲邀擔(dān)任美國(guó)化學(xué)會(huì)Journal of Chemistry Theory and Computation（JCTC）副主編、Theoretical Chemistry Accounts（TCA）、Journal of Theoretical and Computation Chemistry（JTCC）等國(guó)際期刊的高級(jí)編輯。
高加力教授已在Science, Chem. Rev., Acc. Chem. Res, PNAS, Angew. Chem. Int. Ed.和JACS等國(guó)際著名刊物上發(fā)表學(xué)術(shù)論文230余篇，累計(jì)被引用3.6萬(wàn)余次，h-index為76。
報(bào)告內(nèi)容簡(jiǎn)介：
Enzymes are remarkable catalysts that can accelerate the reaction rates as much as 20 orders of magnitude. For example, orotidine 5'-monophosphate decarboxylase (OMPDC) catalyzes the exchange of CO2 for a proton at the C6 position to form uridine 5'-monophosphate (UMP) with a rate increase of 1017 relative to the uncatalyzed reaction. In this talk, I will present analysis of the effect of protein dynamic fluctuations from combined quantum mechanical and molecular mechanical simulations of two proteins. It was found that specific dynamic motions of the proteins are intimately coupled to the function and catalytic mechanism of the catalyzed reactions, by directly affect activation barrier and by controlling the access of water in the active site. In one case, even small changes in the position of the substrate OMP could increase the barrier height by 5 to 10 kcal/mol due to hydrogen bonding interactions. In the LOV domain, a photoreceptor protein, distance mutations significant alter a gating mechanism for water access in the active site and its dark-state recover rate. Analyses of molecular dynamics trajectories help reveal the interplay of protein conformational dynamics and access of water in the active center of the proteins.
