报告题目：Understanding the Binding Specificities of Selectins with 6 and 6’-sulfo sLex
Selectin is a family of cell adhesion molecules that plays a vital role in initiating multicellular adhesive and signaling events during physiological or pathological inflammation and hemostasis. Interactions of selectins with their glycosylated ligands mediate rolling after leucocytes tethered to postcapillary venules in the multistep adhesion cascade. Selectins also transduce signals that modulate leucocyte behavior, and mediate leucocyte adhesion to activated platelets and to other leucocytes. Each selectin (E-, L-, and P-selectin) mediates adhesion in part through interactions of its N-terminal lectin domain with a common sialyl Lewis x (sLex) capping structure (NeuAcα2-3Galβ1-3[Fucα1-3]GlcNAcβ1-R) on cell-surface glycoconjugates. However, as an important derivative, sulfated sLex has expressed different binding specificities with selectins. Experimental measurements have shown 6-sulfo sLex (NeuAcα2-3Galβ1-3[Fucα1-3]GlcNAcβ[SO3--6]1-R) binds to P- and L-selectins stronger than sLex, unlike their comparable binding strengths with E-selectin; 6’-sulfo sLex (NeuAcα2-3Galβ[SO3--6]1-3[Fucα1-3]GlcNAcβ1-R) does not bind to selectins. In this report, molecular models for selectin/sLex and sulfo-sLex complexes were generated to understand the unknown mechanisms for these binding specificities. Theoretical derived interaction energies for selectin and mutated selectin complexes indicated that R46 and K111 are likely to be responsible for binding strength differences of 6-sulfo sLex; the non-binding from 6’-sulfo sLex are probably due to the repulsions between the sulfate group in ligand and E92 and E107 in selectins. The mechanism revealed casts new light on the design of selectin ligands for higher affinities, and lays groundwork for further rational drug design.
王晓聪，2015年毕业于University of Georgia，攻读博士学位期间在Dr. Robert J. Woods的研究组学习糖分子和生物大分子的相互作用，并利用分子模型计算其亲合能，为药物设计提供理论基础与预测。同时，深入学习分子动力学的力场参数开发，并为戊糖提供一套全新的力场参数。毕业后，与哈佛大学的知名教授合作，深入研究选择蛋白和糖分子的相互作用，揭示了选择蛋白配体的专一性，为下一步的药物设计打下理论基础。
2016.2-至今 博士后，University of Georgia ，生物信息学， 分子动力学， 药物设计
2007.8-2015.12 博士，University of Georgia ，生物信息学，分子动力学，药物设计